Template:2020 New References

From Embryology
2020 New References (Expand to see list) 
Mark Hill (talk) 15:48, 8 January 2020 (AEDT) Added this new page to capture updated references added throughout the site in the "Some Recent Findings". Entries are listed alphabetically by topic page. Note that not all new references may be added to this current list. (More? New)
second trimester
  • Morphometric development of the human fetal cerebellum during the early second trimester[1] "The protracted nature of development makes the cerebellum vulnerable to a broad spectrum of pathologic conditions, especially during the early fetal period. This study aims to characterize normal cerebellar growth in human fetuses during the early second trimester. We manually segmented the fetal cerebellum using 7.0-T high-resolution MR images obtained in 35 specimens with gestational ages ranging from 15 to 22 weeks. Volume measurements and shape analysis were performed to quantitatively evaluate global and regional cerebellar growth. The absolute volume of the fetal cerebellum showed a quadratic growth with increasing gestational age, while the pattern of relative volume changes revealed that the cerebellum grew at a greater pace than the cerebrum after 17 gestational weeks. Shape analysis was used to examine the distinctive development of subregions of the cerebellum. The extreme lateral portions of both cerebellar hemispheres showed the lowest rate of growth. The anterior lobe grew faster than most of the posterior lobe. These findings expand our understanding of the early growth pattern of the human cerebellum and could be further used to assess the developmental conditions of the fetal brain."
cortex
  • The genetic architecture of the human cerebral cortex[2] "The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder."
Fetal Alcohol Syndrome
  • Chronic Binge Alcohol Exposure During Pregnancy Alters mTOR System in Rat Fetal hippocampus[3] "We conclude that chronic binge alcohol exposure during pregnancy alters mTORC1 signaling pathway in the fetal hippocampus. We conjecture that this dysregulation of mTOR protein expression, its activity, and downstream proteins may play a critical role in FASD neurobiological phenotypes."
  • In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques[4] "Early diagnosis of fetal alcohol spectrum disorder (FASD) is necessary for initiating early therapy, and is the most effective way to reduce risk of long-term adverse outcomes. This study utilized a nonhuman primate model of FASD, and is the first to exploit in utero MRI to detect the effects of early-pregnancy drinking on the fetal brain. Alterations in motor-related brain regions become detectable with in utero MRI at the beginning of the third trimester equivalent in human pregnancy. Follow-up electrophysiological measurements demonstrated that the MRI-identified brain abnormalities are associated with aberrant brain function. These findings demonstrate the sensitivity of in utero MRI, and inform future clinical studies on the timing and brain region of greatest sensitivity to early ethanol exposure."
fly | molecular
  • Multimodal transcriptional control of pattern formation in embryonic development[5] "Predicting how interactions between transcription factors and regulatory DNA sequence dictate rates of transcription and, ultimately, drive developmental outcomes remains an open challenge in physical biology. Using stripe 2 of the even-skipped gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe and that control of the window of time over which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies (bursting and the time window) respond in different ways to input transcription factor concentrations, suggesting that the stripe is shaped by the interplay of 2 distinct underlying molecular processes."
gestational diabetes | tooth
  • Gestational diabetes mellitus affects odontoblastic differentiation of dental papilla cells via Toll-like receptor 4 signaling in offspring[6] "Gestational diabetes mellitus (GDM) is an important factor involved in the pathogenesis of organ development in the offspring. Here, we analyzed the effects of GDM on odontoblastic differentiation of dental papilla cells (DPCs) and dentin formation in offspring and investigated their underlying mechanisms. A GDM rat model was induced by intraperitoneal injection of streptozotocin and offspring were collected. The results showed that GDM significantly affected odontoblast differentiation and dentin formation in offspring tooth. GDM activated the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-ĸB) signaling pathway and inhibited SMAD1/5/9 signaling to modulate the odontoblastic differentiation of DPCs in offspring. Inhibition of TLR4 signaling by treated with TAK-242 significantly reverses the suppression of odonto-differentiation of DPCs in diabetic offspring. Taken together, these data indicate GDM activated the offspring DPCs TLR4/NF-ĸB signaling, which suppressed the SMAD1/5/9 phosphorylation and then inhibited odontoblasts differentiation and dentin formation." tooth
Hippo
  • Cyclin-Dependent Kinase 7 CDK7 regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus[7] "Hippo signaling controls organ size and tumor progression through a conserved pathway leading to nuclear translocation of the transcriptional effector Yki/Yap/Taz. Most of our understanding of Hippo signaling pertains to its cytoplasmic regulation, but how the pathway is controlled in the nucleus remains poorly understood. Here we uncover an evolutionarily conserved mechanism by which CDK7 promotes Yki/Yap/Taz stabilization in the nucleus to sustain Hippo pathway outputs. We found that a modular E3 ubiquitin ligase complex CRL4DCAF12 binds and targets Yki/Yap/Taz for ubiquitination and degradation, whereas CDK7 phosphorylates Yki/Yap/Taz at S169/S128/S90 to inhibit CRL4DCAF12 recruitment, leading to Yki/Yap/Taz stabilization. As a consequence, inactivation of CDK7 reduced organ size and inhibited tumor growth, which could be reversed by restoring Yki/Yap activity. Our study identifies an unanticipated layer of Hippo pathway regulation, defines a novel mechanism by which CDK7 regulates tissue growth, and implies CDK7 as a drug target for Yap/Taz-driven cancer." OMIM - CDK7
limb | Hox
  • The formation of the thumb requires direct modulation of Gli3 transcription by Hoxa13[8] "In the tetrapod limb, the digits (fingers or toes) are the elements most subject to morphological diversification in response to functional adaptations. However, despite their functional importance, the mechanisms controlling digit morphology remain poorly understood. Here we have focused on understanding the special morphology of the thumb (digit 1), the acquisition of which was an important adaptation of the human hand. To this end, we have studied the limbs of the Hoxa13 mouse mutant that specifically fail to form digit 1. We show that, consistent with the role of Hoxa13 in Hoxd transcriptional regulation, the expression of Hoxd13 in Hoxa13 mutant limbs does not extend into the presumptive digit 1 territory, which is therefore devoid of distal Hox transcripts, a circumstance that can explain its agenesis. The loss of Hoxd13 expression, exclusively in digit 1 territory, correlates with increased Gli3 repressor activity, a Hoxd negative regulator, resulting from increased Gli3 transcription that, in turn, is due to the release from the negative modulation exerted by Hox13 paralogs on Gli3 regulatory sequences. Our results indicate that Hoxa13 acts hierarchically to initiate the formation of digit 1 by reducing Gli3 transcription and by enabling expansion of the 5'Hoxd second expression phase, thereby establishing anterior-posterior asymmetry in the handplate. Our work uncovers a mutual antagonism between Gli3 and Hox13 paralogs that has important implications for Hox and Gli3 gene regulation in the context of development and evolution." limb
inner ear
  • Characterization of the development of the mouse cochlear epithelium at the single cell level[9] "Mammalian hearing requires the development of the organ of Corti, a sensory epithelium comprising unique cell types. The limited number of each of these cell types, combined with their close proximity, has prevented characterization of individual cell types and/or their developmental progression. To examine cochlear development more closely, we transcriptionally profile approximately 30,000 isolated mouse cochlear cells collected at four developmental time points. Here we report on the analysis of those cells including the identification of both known and unknown cell types. Trajectory analysis for OHCs indicates four phases of gene expression while fate mapping of progenitor cells suggests that OHCs and their surrounding supporting cells arise from a distinct (lateral) progenitor pool. Tgfβr1 is identified as being expressed in lateral progenitor cells and a Tgfβr1 antagonist inhibits OHC development."
malaria
  • Malaria in Pregnancy and Adverse Birth Outcomes: New Mechanisms and Therapeutic Opportunities[10] "malaria infection during pregnancy is associated with adverse birth outcomes but underlying mechanisms are poorly understood. Here, we discuss the impact of malaria in pregnancy on three pathways that are important regulators of healthy pregnancy outcomes: L-arginine-nitric oxide biogenesis, complement activation, and the heme axis. These pathways are not mutually exclusive, and they collectively create a proinflammatory, antiangiogenic milieu at the maternal-fetal interface that interferes with placental function and development. We hypothesize that targeting these host-response pathways would mitigate the burden of adverse birth outcomes attributable to malaria in pregnancy."
mammary gland
  • Fry Is Required for mammary gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells[11] "The Fry gene, located on chromosome 13, is an evolutionarily conserved large protein from yeast to human. Our previous study genetically linked the Fry gene with differential susceptibility to mammary carcinogenesis, but whether Fry affects mammary gland development and function, as well as the growth of breast cancer cells, is largely unknown. To define the consequences of Fry loss in the mammary glands, we have generated mice conditionally deficient of the Fry gene in the mammary glands using the Cre-loxP recombination system. We examined multiple phenotypes with male and female homozygous Fry conditional knockout mice (Mfry) and control mice (WT), including body weight, preliminary observations (health and neurological flexes), open field locomotion, sensory abilities, auditory threshold, and glucose metabolism. The loss of Fry in the mammary glands didn't cause a significant difference in these genotypes between Mfry and WT mice. However, our data showed that Fry was required during pregnancy, while it was functionally dispensable in virgin mammary gland development. Loss of Fry led to more lateral buds, and the lobuloalveoli were smaller and showed undistended morphology in mammary glands during late pregnancy. in vitro experiment, ectopic expression of FRY could alter the morphology and significantly suppress the growth and proliferation of the breast cancer cell lines, MDA-MB-231 (ER-/PR-/HER2-, Basal-like) and BT474 (ER+/PR+/HER2+, Luminal B). The following genome-wide transcriptomic analysis of these cells suggested that FRY interacted with protein kinases relevant signaling pathways and induced massive changes in gene expression, including the activation of the Hippo/Yap pathway. Together, our data suggest that the FRY is required for mammary glands developments during pregnant periods, and affects breast cancer cell growth and proliferation."
menstrual cycle | hippocampus,
  • Human menstrual cycle variation in subcortical functional brain connectivity: a multimodal analysis approach[12] "Increasing evidence suggests that endogenous sex steroid changes affect human brain functional connectivity, which could be obtained by resting-state fMRI (RS-fMRI). Nevertheless, RS studies on the menstrual cycle (MC) are underrepresented and yield inconsistent results. We attribute these inconsistencies to the use of various methods in exploratory approaches and small sample sizes. Hormonal fluctuations along the MC likely elicit subtle changes that, however, may still have profound impact on network dynamics when affecting key brain nodes. To address these issues, we propose a ROI-based multimodal analysis approach focusing on areas of high functional relevance to adequately capture these changes. To that end, sixty naturally cycling women underwent RS-fMRI in three different cycle phases and we performed the following analyses: (1) group-independent component analyses to identify intrinsic connectivity networks, (2) eigenvector centrality (EC) as a measure of centrality in the global connectivity hierarchy, (3) amplitude of low-frequency fluctuations (ALFF) as a measure of oscillatory activity and (4) seed-based analyses to investigate functional connectivity from the ROIs. For (2)-(4), we applied a hypothesis-driven ROI approach in the hippocampus, caudate and putamen. In the luteal phase, we found (1) decreased intrinsic connectivity of the right angular gyrus with the default mode network, (2) heightened EC for the hippocampus, and (3) increased ALFF for the caudate. Furthermore, we observed (4) stronger putamen-thalamic connectivity during the luteal phase and stronger fronto-striatal connectivity during the pre-ovulatory phase. This hormonal modulation of connectivity dynamics may underlie behavioural, emotional and sensorimotor changes along the MC."
renal
  • A practical guide to the stereological assessment of glomerular number, size, and cellular composition[13] "The evaluation of a range of measures in the kidneys, such as developmental stage, rate and success, injury, and disease processes, relies on obtaining information on the three-dimensional structure of the renal corpuscles, and in particular the glomerular capillary tufts. To do this in the most accurate, comprehensive, and unbiased manner depends on a knowledge of stereological methods. In this article, we provide a practical guide for researchers on how to quantitate a number of structures in the kidneys, including the estimation of total glomerular number, glomerular capillary length and filtration surface area, and the cellular composition of individual glomeruli. Guidance is also provided on how to apply these methods to kidneys at different sizes and levels of maturity."
somitogenesis | mesoderm
  • In vitro characterization of the human segmentation clock[14] "The segmental organization of the vertebral column is established early in embryogenesis, when pairs of somites are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock. Although this oscillator has been well-characterized in model organisms1,2, whether a similar oscillator exists in humans remains unknown. Genetic analyses of patients with severe spine segmentation defects have implicated several human orthologues of cyclic genes that are associated with the mouse segmentation clock, suggesting that this oscillator might be conserved in humans. Here we show that human PSM cells derived in vitro-as well as those of the mouse4-recapitulate the oscillations of the segmentation clock. Human PSM cells oscillate with a period two times longer than that of mouse cells (5 h versus 2.5 h), but are similarly regulated by FGF, WNT, Notch and YAP signalling5. Single-cell RNA sequencing reveals that mouse and human PSM cells in vitro follow a developmental trajectory similar to that of mouse PSM in vivo. Furthermore, we demonstrate that FGF signalling controls the phase and period of oscillations, expanding the role of this pathway beyond its classical interpretation in 'clock and wavefront' models1. Our work identifying the human segmentation clock represents an important milestone in understanding human developmental biology."
  • Coupling delay controls synchronized oscillation in the segmentation clock[15] "Individual cellular activities fluctuate but are constantly coordinated at the population level via cell-cell coupling. A notable example is the somite segmentation clock, in which the expression of clock genes (such as Hes7) oscillates in synchrony between the cells that comprise the presomitic mesoderm (PSM)1,2. This synchronization depends on the Notch signalling pathway; inhibiting this pathway desynchronizes oscillations, leading to somite fusion3-7. However, how Notch signalling regulates the synchronicity of HES7 oscillations is unknown. Here we establish a live-imaging system using a new fluorescent reporter (Achilles), which we fuse with HES7 to monitor synchronous oscillations in HES7 expression in the mouse PSM at a single-cell resolution. Wild-type cells can rapidly correct for phase fluctuations in HES7 oscillations, whereas the absence of the Notch modulator gene lunatic fringe (Lfng) leads to a loss of synchrony between PSM cells. Furthermore, HES7 oscillations are severely dampened in individual cells of Lfng-null PSM. However, when Lfng-null PSM cells were completely dissociated, the amplitude and periodicity of HES7 oscillations were almost normal, which suggests that LFNG is involved mostly in cell-cell coupling. Mixed cultures of control and Lfng-null PSM cells, and an optogenetic Notch signalling reporter assay, revealed that LFNG delays the signal-sending process of intercellular Notch signalling transmission. These results-together with mathematical modelling-raised the possibility that Lfng-null PSM cells shorten the coupling delay, thereby approaching a condition known as the oscillation or amplitude death of coupled oscillators8. Indeed, a small compound that lengthens the coupling delay partially rescues the amplitude and synchrony of HES7 oscillations in Lfng-null PSM cells. Our study reveals a delay control mechanism of the oscillatory networks involved in somite segmentation, and indicates that intercellular coupling with the correct delay is essential for synchronized oscillation."
zebrafish
  • Conserved Genoarchitecture of the Basal Hypothalamus in zebrafish Embryos[16] "Analyses of genoarchitecture recently stimulated substantial revisions of anatomical models for the developing hypothalamus‎ in mammalian and other vertebrate systems. The prosomeric model proposes the hypothalamus to be derived from the secondary prosencephalon, and to consist of alar and basal regions. The basal hypothalamus can further be subdivided into tuberal and mamillary regions, each with distinct subregions. ...Our comparison of gene expression patterns reveals that the genoarchitecture of the basal hypothalamus in zebrafish embryos 48 hours post fertilization is highly similar to mouse embryos at E13.5. We found the tuberal hypothalamus in zebrafish embryos to be relatively large and to comprise previously ill-defined regions around the posterior hypothalamic recess. The mamillary hypothalamus is smaller and concentrates to rather medial areas in proximity to the anterior end of the neural tube floor plate. Within the basal hypothalamus we identified longitudinal and transverse tuberal and mamillary subregions topologically equivalent to those previously described in other vertebrates. However, the hypothalamic diencephalic boundary region and the posterior tuberculum still provide a challenge."
References
  1. Xu F, Ge X, Shi Y, Zhang Z, Tang Y, Lin X, Teng G, Zang F, Gao N, Liu H, Toga AW & Liu S. (2020). Morphometric development of the human fetal cerebellum during the early second trimester. Neuroimage , 207, 116372. PMID: 31751665 DOI.
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  3. Lee J, Lunde-Young R, Naik V, Ramirez J, Orzabal M & Ramadoss J. (2020). Chronic Binge Alcohol Exposure During Pregnancy Alters mTOR System in Rat Fetal Hippocampus. Alcohol. Clin. Exp. Res. , , . PMID: 32333810 DOI.
  4. Wang X, Cuzon Carlson VC, Studholme C, Newman N, Ford MM, Grant KA & Kroenke CD. (2020). In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques. Proc. Natl. Acad. Sci. U.S.A. , 117, 10035-10044. PMID: 32312804 DOI.
  5. Lammers NC, Galstyan V, Reimer A, Medin SA, Wiggins CH & Garcia HG. (2020). Multimodal transcriptional control of pattern formation in embryonic development. Proc. Natl. Acad. Sci. U.S.A. , 117, 836-847. PMID: 31882445 DOI.
  6. Lyu Y, Jia S, Wang S, Wang T, Tian W & Chen G. (2020). Gestational diabetes mellitus affects odontoblastic differentiation of dental papilla cells via Toll-like receptor 4 signaling in offspring. J. Cell. Physiol. , 235, 3519-3528. PMID: 31595494 DOI.
  7. Cho YS, Li S, Wang X, Zhu J, Zhuo S, Han Y, Yue T, Yang Y & Jiang J. (2020). CDK7 regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus. Genes Dev. , 34, 53-71. PMID: 31857346 DOI.
  8. Bastida MF, Pérez-Gómez R, Trofka A, Zhu J, Rada-Iglesias A, Sheth R, Stadler HS, Mackem S & Ros MA. (2020). The formation of the thumb requires direct modulation of Gli3 transcription by Hoxa13. Proc. Natl. Acad. Sci. U.S.A. , 117, 1090-1096. PMID: 31896583 DOI.
  9. Kolla L, Kelly MC, Mann ZF, Anaya-Rocha A, Ellis K, Lemons A, Palermo AT, So KS, Mays JC, Orvis J, Burns JC, Hertzano R, Driver EC & Kelley MW. (2020). Characterization of the development of the mouse cochlear epithelium at the single cell level. Nat Commun , 11, 2389. PMID: 32404924 DOI.
  10. Ngai M, Weckman AM, Erice C, McDonald CR, Cahill LS, Sled JG & Kain KC. (2020). Malaria in Pregnancy and Adverse Birth Outcomes: New Mechanisms and Therapeutic Opportunities. Trends Parasitol. , 36, 127-137. PMID: 31864896 DOI.
  11. Liu Y, Chen X, Gong Z, Zhang H, Fei F, Tang X, Wang J, Xu P, Zarbl H & Ren X. (2019). Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells. Front Oncol , 9, 1279. PMID: 31824855 DOI.
  12. Hidalgo-Lopez E, Mueller K, Harris T, Aichhorn M, Sacher J & Pletzer B. (2020). Human menstrual cycle variation in subcortical functional brain connectivity: a multimodal analysis approach. Brain Struct Funct , , . PMID: 31894405 DOI.
  13. Sutherland MR, Vojisavljevic D & Black MJ. (2020). A practical guide to the stereological assessment of glomerular number, size, and cellular composition. Anat Rec (Hoboken) , , . PMID: 31960613 DOI.
  14. Diaz-Cuadros M, Wagner DE, Budjan C, Hubaud A, Tarazona OA, Donelly S, Michaut A, Al Tanoury Z, Yoshioka-Kobayashi K, Niino Y, Kageyama R, Miyawaki A, Touboul J & Pourquié O. (2020). In vitro characterization of the human segmentation clock. Nature , , . PMID: 31915384 DOI.
  15. Yoshioka-Kobayashi K, Matsumiya M, Niino Y, Isomura A, Kori H, Miyawaki A & Kageyama R. (2020). Coupling delay controls synchronized oscillation in the segmentation clock. Nature , , . PMID: 31915376 DOI.
  16. Schredelseker T & Driever W. (2020). Conserved Genoarchitecture of the Basal Hypothalamus in Zebrafish Embryos. Front Neuroanat , 14, 3. PMID: 32116574 DOI.