Developmental Signals - Bone Morphogenetic Protein - Revision history

Z8600021 at 02:58, 23 February 2022

2022-02-23T02:58:31Z

← Older revision		Revision as of 13:58, 23 February 2022
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			* '''Pharyngeal pouches provide a niche microenvironment for arch artery progenitor specification'''{{#pmid:33334861\|PMID33334861}} "The paired pharyngeal arch arteries (PAAs) are transient blood vessels connecting the heart with the dorsal aorta during embryogenesis. Although PAA malformations often occur along with pharyngeal pouch defects, the functional interaction between these adjacent tissues remains largely unclear. Here, we report that pharyngeal pouches are essential for PAA progenitor specification in zebrafish embryos. We reveal that the segmentation of pharyngeal pouches coincides spatiotemporally with the emergence of PAA progenitor clusters. These pouches physically associate with pharyngeal mesoderm in discrete regions and provide a niche microenvironment for PAA progenitor commitment by expressing BMP proteins. Specifically, pouch-derived BMP2a and BMP5 are the primary niche cues responsible for activating the BMP/Smad pathway in pharyngeal mesoderm, thereby promoting progenitor specification. In addition, BMP2a and BMP5 play an inductive function in the expression of the cloche gene npas4l in PAA progenitors. cloche mutants exhibit a striking failure to specify PAA progenitors and display ectopic expression of head muscle markers in the pharyngeal mesoderm. Therefore, our results support a crucial role for pharyngeal pouches in establishing a progenitor niche for PAA morphogenesis via BMP2a/5 expression."

	* '''Opening the Black Box - Stem Cell-Based Modeling of Human Post-Implantation Development'''{{#pmid:30552099\|PMID30552099}} "Proper development of the human embryo following its {{implantation}} into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)-based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development." {{gastrulation}}		* '''Opening the Black Box - Stem Cell-Based Modeling of Human Post-Implantation Development'''{{#pmid:30552099\|PMID30552099}} "Proper development of the human embryo following its {{implantation}} into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)-based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development." {{gastrulation}}

Z8600021 at 07:21, 7 December 2021

2021-12-07T07:21:45Z

← Older revision		Revision as of 18:21, 7 December 2021
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	* '''Opening the Black Box - Stem Cell-Based Modeling of Human Post-Implantation Development'''{{#pmid:30552099\|PMID30552099}} "Proper development of the human embryo following its {{implantation}} into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)-based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development." {{gastrulation}}		* '''Opening the Black Box - Stem Cell-Based Modeling of Human Post-Implantation Development'''{{#pmid:30552099\|PMID30552099}} "Proper development of the human embryo following its {{implantation}} into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)-based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development." {{gastrulation}}

	* '''Serum concentrations of oocyte-secreted factors BMP15 and GDF9 during IVF and in women with reproductive pathologies'''{{#pmid:31211369\|PMID31211369}} "Oocyte-secreted factors, bone morphogenetic protein-15 ({{BMP}}15) and growth differentiation factor-9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function. Serum samples were obtained from women undergoing infertility treatments (n=154), and from peri- and post-menopausal women (n=28). Serum concentrations of BMP15 and GDF9 in women relative to age, AMH, number of oocytes retrieved, and polycystic ovaries/syndrome (PCO(S)) after superovulation for IVF. BMP15 and GDF9 immunoassays were validated for specificity, sensitivity (24 and 26 pg/ml, respectively) and reproducibility. BMP15 and GDF9 were detectable in 61% and 29% of women, respectively. BMP15 and GDF9 varied 64- and 15-fold respectively between women, but did not change within subjects following ovarian stimulation with gonadotropins. Serum GDF9 concentration, but not BMP15, was associated with oocyte number retrieved in non-PCO(S) patients (p=0.018). GDF9 and BMP15 associations with oocyte number differed significantly (p<0.05) with PCO(S) status. GDF9 concentrations were lower in poor responders (women with <4 oocytes retrieved or cancelled cycles; p=0.020). Serum BMP15, but not GDF9, was lower in women over 55 years, compared to women of reproductive age (p<0.01). This study develops and validates immunoassays to quantitate BMP15 and GDF9 in human serum, and to correlate concentrations with female reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine."		* '''Serum concentrations of oocyte-secreted factors BMP15 and GDF9 during IVF and in women with reproductive pathologies'''{{#pmid:31211369\|PMID31211369}} "Oocyte-secreted factors, bone morphogenetic protein-15 ({{BMP}}15) and growth differentiation factor-9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function."

	* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling."		* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate."
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Z8600021 at 07:20, 7 December 2021

2021-12-07T07:20:27Z

← Older revision		Revision as of 18:20, 7 December 2021
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	* '''Opening the Black Box - Stem Cell-Based Modeling of Human Post-Implantation Development'''{{#pmid:30552099\|PMID30552099}} "Proper development of the human embryo following its {{implantation}} into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)-based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development." {{gastrulation}}		* '''Opening the Black Box - Stem Cell-Based Modeling of Human Post-Implantation Development'''{{#pmid:30552099\|PMID30552099}} "Proper development of the human embryo following its {{implantation}} into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)-based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development." {{gastrulation}}

	* '''Serum concentrations of oocyte-secreted factors BMP15 and GDF9 during IVF and in women with reproductive pathologies'''{{#pmid:31211369}} "Oocyte-secreted factors, bone morphogenetic protein-15 ({{BMP}}15) and growth differentiation factor-9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function. Serum samples were obtained from women undergoing infertility treatments (n=154), and from peri- and post-menopausal women (n=28). Serum concentrations of BMP15 and GDF9 in women relative to age, AMH, number of oocytes retrieved, and polycystic ovaries/syndrome (PCO(S)) after superovulation for IVF. BMP15 and GDF9 immunoassays were validated for specificity, sensitivity (24 and 26 pg/ml, respectively) and reproducibility. BMP15 and GDF9 were detectable in 61% and 29% of women, respectively. BMP15 and GDF9 varied 64- and 15-fold respectively between women, but did not change within subjects following ovarian stimulation with gonadotropins. Serum GDF9 concentration, but not BMP15, was associated with oocyte number retrieved in non-PCO(S) patients (p=0.018). GDF9 and BMP15 associations with oocyte number differed significantly (p<0.05) with PCO(S) status. GDF9 concentrations were lower in poor responders (women with <4 oocytes retrieved or cancelled cycles; p=0.020). Serum BMP15, but not GDF9, was lower in women over 55 years, compared to women of reproductive age (p<0.01). This study develops and validates immunoassays to quantitate BMP15 and GDF9 in human serum, and to correlate concentrations with female reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine."		* '''Serum concentrations of oocyte-secreted factors BMP15 and GDF9 during IVF and in women with reproductive pathologies'''{{#pmid:31211369\|PMID31211369}} "Oocyte-secreted factors, bone morphogenetic protein-15 ({{BMP}}15) and growth differentiation factor-9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function. Serum samples were obtained from women undergoing infertility treatments (n=154), and from peri- and post-menopausal women (n=28). Serum concentrations of BMP15 and GDF9 in women relative to age, AMH, number of oocytes retrieved, and polycystic ovaries/syndrome (PCO(S)) after superovulation for IVF. BMP15 and GDF9 immunoassays were validated for specificity, sensitivity (24 and 26 pg/ml, respectively) and reproducibility. BMP15 and GDF9 were detectable in 61% and 29% of women, respectively. BMP15 and GDF9 varied 64- and 15-fold respectively between women, but did not change within subjects following ovarian stimulation with gonadotropins. Serum GDF9 concentration, but not BMP15, was associated with oocyte number retrieved in non-PCO(S) patients (p=0.018). GDF9 and BMP15 associations with oocyte number differed significantly (p<0.05) with PCO(S) status. GDF9 concentrations were lower in poor responders (women with <4 oocytes retrieved or cancelled cycles; p=0.020). Serum BMP15, but not GDF9, was lower in women over 55 years, compared to women of reproductive age (p<0.01). This study develops and validates immunoassays to quantitate BMP15 and GDF9 in human serum, and to correlate concentrations with female reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine."

	* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling."		* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling."

Z8600021 at 07:17, 7 December 2021

2021-12-07T07:17:08Z

← Older revision		Revision as of 18:17, 7 December 2021
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	* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling."		* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling."

	* '''Bmp4 is an essential growth factor for the initiation of {{genita}}l tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}} "The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth." {{genital}}
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			* '''Bmp4 is an essential growth factor for the initiation of {{genital}} tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}} "The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth." {{genital}}

	* '''{{BMP}} and {{FGF}} signaling interact to pattern {{mesoderm}} by controlling basic helix-loop-helix transcription factor activity'''{{#pmid:29877796\|PMID29877796}} "The {{mesoderm}}al germ layer is patterned into mediolateral subtypes by signaling factors including {{BMP}} and {{FGF}}. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer."		* '''{{BMP}} and {{FGF}} signaling interact to pattern {{mesoderm}} by controlling basic helix-loop-helix transcription factor activity'''{{#pmid:29877796\|PMID29877796}} "The {{mesoderm}}al germ layer is patterned into mediolateral subtypes by signaling factors including {{BMP}} and {{FGF}}. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer."

Z8600021 at 07:15, 7 December 2021

2021-12-07T07:15:34Z

← Older revision		Revision as of 18:15, 7 December 2021
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	== Some Recent Findings ==		== Some Recent Findings ==
	[[File:Gastrulation molecular factors01.jpg\|thumb\|alt=Gastrulation molecular factors\|Formation of primary germ layer–like cells in a micropattern platform orchestrated by BMP signaling.{{#pmid:30552099\|PMID30552099}}		[[File:Gastrulation molecular factors01.jpg\|thumb\|alt=Gastrulation molecular factors\|Formation of primary germ layer–like cells in a micropattern platform orchestrated by BMP signaling.{{#pmid:30552099\|PMID30552099}}]]
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Z8600021 at 00:46, 29 Haziran 2020

2020-06-29T00:46:49Z

← Older revision		Revision as of 11:46, 29 Haziran 2020
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	== Some Recent Findings ==		== Some Recent Findings ==
			[[File:Gastrulation molecular factors01.jpg\|thumb\|alt=Gastrulation molecular factors\|Formation of primary germ layer–like cells in a micropattern platform orchestrated by BMP signaling.{{#pmid:30552099\|PMID30552099}}
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Z8600021 at 00:32, 29 Haziran 2020

2020-06-29T00:32:34Z

← Older revision		Revision as of 11:32, 29 Haziran 2020
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	\|		\|
			* '''Opening the Black Box - Stem Cell-Based Modeling of Human Post-Implantation Development'''{{#pmid:30552099\|PMID30552099}} "Proper development of the human embryo following its {{implantation}} into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)-based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development." {{gastrulation}}

	* '''Serum concentrations of oocyte-secreted factors BMP15 and GDF9 during IVF and in women with reproductive pathologies'''{{#pmid:31211369}} "Oocyte-secreted factors, bone morphogenetic protein-15 ({{BMP}}15) and growth differentiation factor-9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function. Serum samples were obtained from women undergoing infertility treatments (n=154), and from peri- and post-menopausal women (n=28). Serum concentrations of BMP15 and GDF9 in women relative to age, AMH, number of oocytes retrieved, and polycystic ovaries/syndrome (PCO(S)) after superovulation for IVF. BMP15 and GDF9 immunoassays were validated for specificity, sensitivity (24 and 26 pg/ml, respectively) and reproducibility. BMP15 and GDF9 were detectable in 61% and 29% of women, respectively. BMP15 and GDF9 varied 64- and 15-fold respectively between women, but did not change within subjects following ovarian stimulation with gonadotropins. Serum GDF9 concentration, but not BMP15, was associated with oocyte number retrieved in non-PCO(S) patients (p=0.018). GDF9 and BMP15 associations with oocyte number differed significantly (p<0.05) with PCO(S) status. GDF9 concentrations were lower in poor responders (women with <4 oocytes retrieved or cancelled cycles; p=0.020). Serum BMP15, but not GDF9, was lower in women over 55 years, compared to women of reproductive age (p<0.01). This study develops and validates immunoassays to quantitate BMP15 and GDF9 in human serum, and to correlate concentrations with female reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine."		* '''Serum concentrations of oocyte-secreted factors BMP15 and GDF9 during IVF and in women with reproductive pathologies'''{{#pmid:31211369}} "Oocyte-secreted factors, bone morphogenetic protein-15 ({{BMP}}15) and growth differentiation factor-9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function. Serum samples were obtained from women undergoing infertility treatments (n=154), and from peri- and post-menopausal women (n=28). Serum concentrations of BMP15 and GDF9 in women relative to age, AMH, number of oocytes retrieved, and polycystic ovaries/syndrome (PCO(S)) after superovulation for IVF. BMP15 and GDF9 immunoassays were validated for specificity, sensitivity (24 and 26 pg/ml, respectively) and reproducibility. BMP15 and GDF9 were detectable in 61% and 29% of women, respectively. BMP15 and GDF9 varied 64- and 15-fold respectively between women, but did not change within subjects following ovarian stimulation with gonadotropins. Serum GDF9 concentration, but not BMP15, was associated with oocyte number retrieved in non-PCO(S) patients (p=0.018). GDF9 and BMP15 associations with oocyte number differed significantly (p<0.05) with PCO(S) status. GDF9 concentrations were lower in poor responders (women with <4 oocytes retrieved or cancelled cycles; p=0.020). Serum BMP15, but not GDF9, was lower in women over 55 years, compared to women of reproductive age (p<0.01). This study develops and validates immunoassays to quantitate BMP15 and GDF9 in human serum, and to correlate concentrations with female reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine."

Line 26:		Line 28:

	* '''Bmp4 is an essential growth factor for the initiation of {{genita}}l tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}} "The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth." {{genital}}		* '''Bmp4 is an essential growth factor for the initiation of {{genita}}l tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}} "The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth." {{genital}}

	* '''{{BMP}} and {{FGF}} signaling interact to pattern {{mesoderm}} by controlling basic helix-loop-helix transcription factor activity'''{{#pmid:29877796\|PMID29877796}} "The {{mesoderm}}al germ layer is patterned into mediolateral subtypes by signaling factors including {{BMP}} and {{FGF}}. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer."

	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
Line 36:		Line 35:

	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Bone+Morphogenetic+Protein ''Bone Morphogenetic Protein''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP ''BMP''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP4 ''BMP4''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP7 ''BMP7''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP15 ''BMP15'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Bone+Morphogenetic+Protein ''Bone Morphogenetic Protein''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP ''BMP''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP4 ''BMP4''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP7 ''BMP7''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP15 ''BMP15'']


	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
Line 43:		Line 40:
	\|-		\|-
	\| {{Older papers}}		\| {{Older papers}}
			* '''{{BMP}} and {{FGF}} signaling interact to pattern {{mesoderm}} by controlling basic helix-loop-helix transcription factor activity'''{{#pmid:29877796\|PMID29877796}} "The {{mesoderm}}al germ layer is patterned into mediolateral subtypes by signaling factors including {{BMP}} and {{FGF}}. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer."

	* '''Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells'''{{#pmid:26934293\|PMID26934293}} "Neural crest (NC) cells are a group of cells located in the neural folds at the boundary between the neural and epidermal ectoderm. Cranial NC cells migrate to the branchial arches and give rise to the majority of the craniofacial region, whereas trunk and tail NC cells contribute to the heart, enteric ganglia of the gut, melanocytes, sympathetic ganglia, and adrenal chromaffin cells. ...These BMP4-treated NC cells were capable of differentiation into osteocytes and chondrocytes. The results of the present study indicate that BMP4 regulates cranial positioning during NC development." {{Neural crest}}		* '''Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells'''{{#pmid:26934293\|PMID26934293}} "Neural crest (NC) cells are a group of cells located in the neural folds at the boundary between the neural and epidermal ectoderm. Cranial NC cells migrate to the branchial arches and give rise to the majority of the craniofacial region, whereas trunk and tail NC cells contribute to the heart, enteric ganglia of the gut, melanocytes, sympathetic ganglia, and adrenal chromaffin cells. ...These BMP4-treated NC cells were capable of differentiation into osteocytes and chondrocytes. The results of the present study indicate that BMP4 regulates cranial positioning during NC development." {{Neural crest}}

Z8600021 at 17:08, 28 Haziran 2020

2020-06-28T17:08:46Z

← Older revision		Revision as of 04:08, 29 Haziran 2020
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	===Articles===		===Articles===
			{{#pmid:30552099}}

	{{#pmid:24698271}}		{{#pmid:24698271}}

Z8600021 at 00:21, 25 Haziran 2019

2019-06-25T00:21:36Z

← Older revision		Revision as of 11:21, 25 Haziran 2019
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	\| [[File:Mark_Hill.jpg\|90px\|left]] {{Most_Recent_Refs}}		\| [[File:Mark_Hill.jpg\|90px\|left]] {{Most_Recent_Refs}}

	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Bone+Morphogenetic+Protein ''Bone Morphogenetic Protein'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Bone+Morphogenetic+Protein ''Bone Morphogenetic Protein''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP ''BMP''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP4 ''BMP4''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP7 ''BMP7''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=BMP15 ''BMP15'']


	\|}		\|}
Line 90:		Line 91:

	==Function==		==Function==
			===BMP4===
	{\|		{\|
	\| [[File:Mouse Bmp4 expression limb and face 01.jpg\|600px]]		\| [[File:Mouse Bmp4 expression limb and face 01.jpg\|600px]]
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	:'''Links:''' [[Neural ~~System~~ Development\|~~Neural Development]]~~		:'''Links:''' {{Neural}}
	===Oocyte Development===
			====Genital Development====

			'''Bmp4 is an essential growth factor for the initiation of {{genita}}l tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}}

			:"The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth."

			:'''Links:''' {{genital}}

			===BMP15===

			====Oocyte Development====

	{\|		{\|
	\| [[File:Ovarian follicle molecular interactions 01.jpg\|300px\|alt=Ovarian follicle molecular interactions]]		\| [[File:Ovarian follicle molecular interactions 01.jpg\|300px\|alt=Ovarian follicle molecular interactions]]
Line 127:		Line 141:
	BMP/SMAD signaling pathway regulates angiogenic sprouting and is involved in embryo vascular development.		BMP/SMAD signaling pathway regulates angiogenic sprouting and is involved in embryo vascular development.

	~~===Genital Development===~~

	~~'''Bmp4 is an essential growth factor for the initiation of {{genita}}l tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}}~~

	:"The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth."

	~~:'''Links:''' {{genital}}~~

	==Signaling Pathway==		==Signaling Pathway==

Z8600021 at 00:17, 25 Haziran 2019

2019-06-25T00:17:48Z

← Older revision		Revision as of 11:17, 25 Haziran 2019
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	\|-bgcolor="F5FAFF"		\|-bgcolor="F5FAFF"
	\|		\|
			* '''Serum concentrations of oocyte-secreted factors BMP15 and GDF9 during IVF and in women with reproductive pathologies'''{{#pmid:31211369}} "Oocyte-secreted factors, bone morphogenetic protein-15 ({{BMP}}15) and growth differentiation factor-9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function. Serum samples were obtained from women undergoing infertility treatments (n=154), and from peri- and post-menopausal women (n=28). Serum concentrations of BMP15 and GDF9 in women relative to age, AMH, number of oocytes retrieved, and polycystic ovaries/syndrome (PCO(S)) after superovulation for IVF. BMP15 and GDF9 immunoassays were validated for specificity, sensitivity (24 and 26 pg/ml, respectively) and reproducibility. BMP15 and GDF9 were detectable in 61% and 29% of women, respectively. BMP15 and GDF9 varied 64- and 15-fold respectively between women, but did not change within subjects following ovarian stimulation with gonadotropins. Serum GDF9 concentration, but not BMP15, was associated with oocyte number retrieved in non-PCO(S) patients (p=0.018). GDF9 and BMP15 associations with oocyte number differed significantly (p<0.05) with PCO(S) status. GDF9 concentrations were lower in poor responders (women with <4 oocytes retrieved or cancelled cycles; p=0.020). Serum BMP15, but not GDF9, was lower in women over 55 years, compared to women of reproductive age (p<0.01). This study develops and validates immunoassays to quantitate BMP15 and GDF9 in human serum, and to correlate concentrations with female reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine."

	* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling."		* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling."

← Older revision		Revision as of 18:21, 7 December 2021
Line 24:		Line 24:
	* '''Opening the Black Box - Stem Cell-Based Modeling of Human Post-Implantation Development'''{{#pmid:30552099\|PMID30552099}} "Proper development of the human embryo following its {{implantation}} into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)-based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development." {{gastrulation}}		* '''Opening the Black Box - Stem Cell-Based Modeling of Human Post-Implantation Development'''{{#pmid:30552099\|PMID30552099}} "Proper development of the human embryo following its {{implantation}} into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)-based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development." {{gastrulation}}

	* '''Serum concentrations of oocyte-secreted factors BMP15 and GDF9 during IVF and in women with reproductive pathologies'''{{#pmid:31211369\|PMID31211369}} "Oocyte-secreted factors, bone morphogenetic protein-15 ({{BMP}}15) and growth differentiation factor-9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function. Serum samples were obtained from women undergoing infertility treatments (n=154), and from peri- and post-menopausal women (n=28). Serum concentrations of BMP15 and GDF9 in women relative to age, AMH, number of oocytes retrieved, and polycystic ovaries/syndrome (PCO(S)) after superovulation for IVF. BMP15 and GDF9 immunoassays were validated for specificity, sensitivity (24 and 26 pg/ml, respectively) and reproducibility. BMP15 and GDF9 were detectable in 61% and 29% of women, respectively. BMP15 and GDF9 varied 64- and 15-fold respectively between women, but did not change within subjects following ovarian stimulation with gonadotropins. Serum GDF9 concentration, but not BMP15, was associated with oocyte number retrieved in non-PCO(S) patients (p=0.018). GDF9 and BMP15 associations with oocyte number differed significantly (p<0.05) with PCO(S) status. GDF9 concentrations were lower in poor responders (women with <4 oocytes retrieved or cancelled cycles; p=0.020). Serum BMP15, but not GDF9, was lower in women over 55 years, compared to women of reproductive age (p<0.01). This study develops and validates immunoassays to quantitate BMP15 and GDF9 in human serum, and to correlate concentrations with female reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine."		* '''Serum concentrations of oocyte-secreted factors BMP15 and GDF9 during IVF and in women with reproductive pathologies'''{{#pmid:31211369\|PMID31211369}} "Oocyte-secreted factors, bone morphogenetic protein-15 ({{BMP}}15) and growth differentiation factor-9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function."

	* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling."		* '''BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates'''{{#pmid:31189599\|PMID31189599}} "A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate."
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"