Talk:Developmental Signals - TGF-beta

From Embryology
About Discussion Pages  
Mark Hill.jpg
On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes:
  1. References - recent and historic that relates to the topic
  2. Additional topic information - currently prepared in draft format
  3. Links - to related webpages
  4. Topic page - an edit history as used on other Wiki sites
  5. Lecture/Practical - student feedback
  6. Student Projects - online project discussions.
Links: Pubmed Most Recent | Reference Tutorial | Journal Searches

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2024, June 14) Embryology Developmental Signals - TGF-beta. Retrieved from


Prenatal nicotine exposure increases osteoarthritis susceptibility in male elderly offspring rats via low-function programming of the TGFβ signaling pathway

Toxicol Lett. 2019 Jul 9. pii: S0378-4274(19)30180-8. doi: 10.1016/j.toxlet.2019.06.010. [Epub ahead of print]

Chen B1, Lu KH1, Ni QB1, Li QX1, Gao H1, Wang H2, Chen LB3.

Epidemiological investigations indicate that effects related to prenatal adverse environments on the organs of the offspring could continue to adulthood. This study intends to confirm that prenatal nicotine exposure (PNE) increases the susceptibility of osteoarthritis (OA) in the male offspring, and to explore the potential intrauterine programming mechanism. During pregnancy, rats were divided into a PNE group and a control group. After birth, rats were given a high-fat diet for 6 months and long-distance running for 6 weeks. The rats were euthanized at 18 months after birth (PM18) and on gestational day 20 (GD20), respectively. Knee joints were collected for histochemistry, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) assays. Histological analyses and the Mankin's score showed increased cartilage destruction and accelerated OA progression in adult offspring from the PNE group. Immunohistochemistry results showed decreased expression of transforming growth factor beta (TGFβ) signaling pathway. Furthermore, the expression of apoptosis factors (caspase-3 and caspase-8), inflammatory factors [interleukin (IL)-1, IL-6] and matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13] were also significantly increased. Traced back to the intrauterine period, it was found that the number of chondrocytes and the contents of Col2A1 and aggrecan in the matrix in the PNE group were decreased. And, the expression of the TGFβ signaling pathway was inhibited. These results suggested that PNE enhanced the susceptibility of OA in male elderly offspring rats by down-regulating TGFβ signaling, which increased articular cartilage local inflammation, matrix degradation, and cell apoptosis. This study confirmed the developmental origin of OA, and clarified the congenital and the living environment impact on the occurrence and development of OA. Our findings provide a theoretical and experimental basis for OA early prevention. Copyright © 2019. Published by Elsevier B.V. KEYWORDS: TGFβ signaling pathway; inflammation; intrauterine programming; osteoarthritis; prenatal nicotine exposure PMID: 31299270 DOI: 10.1016/j.toxlet.2019.06.010


TGF-β Family Signaling in Early Vertebrate Development

Cold Spring Harb Perspect Biol. 2018 Jun 1;10(6). pii: a033274. doi: 10.1101/cshperspect.a033274.

Zinski J1, Tajer B1, Mullins MC1.

Abstract TGF-β family ligands function in inducing and patterning many tissues of the early vertebrate embryonic body plan. Nodal signaling is essential for the specification of mesendodermal tissues and the concurrent cellular movements of gastrulation. Bone morphogenetic protein (BMP) signaling patterns tissues along the dorsal-ventral axis and simultaneously directs the cell movements of convergence and extension. After gastrulation, a second wave of Nodal signaling breaks the symmetry between the left and right sides of the embryo. During these processes, elaborate regulatory feedback between TGF-β ligands and their antagonists direct the proper specification and patterning of embryonic tissues. In this review, we summarize the current knowledge of the function and regulation of TGF-β family signaling in these processes. Although we cover principles that are involved in the development of all vertebrate embryos, we focus specifically on three popular model organisms: the mouse Mus musculus, the African clawed frog of the genus Xenopus, and the zebrafish Danio rerio, highlighting the similarities and differences between these species. PMID: 28600394 DOI: 10.1101/cshperspect.a033274


A new developmental mechanism for the separation of the mammalian middle ear ossicles from the jaw

Proc Biol Sci. 2017 Feb 8;284(1848). pii: 20162416. doi: 10.1098/rspb.2016.2416.

Urban DJ1, Anthwal N2, Luo ZX3, Maier JA1, Sadier A1, Tucker AS2, Sears KE4,5.


Multiple mammalian lineages independently evolved a definitive mammalian middle ear (DMME) through breakdown of Meckel's cartilage (MC). However, the cellular and molecular drivers of this evolutionary transition remain unknown for most mammal groups. Here, we identify such drivers in the living marsupial opossum Monodelphis domestica, whose MC transformation during development anatomically mirrors the evolutionary transformation observed in fossils. Specifically, we link increases in cellular apoptosis and TGF-BR2 signalling to MC breakdown in opossums. We demonstrate that a simple change in TGF-β signalling is sufficient to inhibit MC breakdown during opossum development, indicating that changes in TGF-β signalling might be key during mammalian evolution. Furthermore, the apoptosis that we observe during opossum MC breakdown does not seemingly occur in mouse, consistent with homoplastic DMME evolution in the marsupial and placental lineages. © 2017 The Author(s). KEYWORDS: Meckel's cartilage; TGFB signalling; apoptosis; marsupial; origin of mammals

PMID 28179517 DOI: 10.1098/rspb.2016.2416


Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases gap junction intercellular communication activity in immortalized human granulosa cells

Mol Hum Reprod. 2014 Jan 26. [Epub ahead of print]

Chang HM, Cheng JC, Taylor E, Leung PC. Author information

Abstract In the ovary, connexin-coupled gap junctions in granulosa cells play crucial roles in follicular and oocyte development as well as in corpus luteum formation. Our previous work has shown that theca cell-derived bone morphogenetic protein (BMP)4 and BMP7 decrease gap junction intercellular communication (GJIC) activity via the down-regulation of connexin43 (Cx43) expression in immortalized human granulosa cells. However, the effects of oocyte-derived growth factors on Cx43 expression remain to be elucidated. The present study was designed to investigate the effects of oocyte-derived growth differentiation factor (GDF)9 and BMP15 on the expression of Cx43 in a human granulosa cell line, SVOG. We also examined the effect relative to GJIC activity and investigated the potential mechanisms of action. In SVOG cells, treatment with BMP15 but not GDF9 significantly decreased Cx43 mRNA and protein levels and GJIC activity. These suppressive effects, along with the induction of Smad1/5/8 phosphorylation, were attenuated by co-treatment with a BMP type I receptor inhibitor, dorsomorphin. Furthermore, knockdown of the central component of the transforming growth factor-β superfamily signaling pathway, Smad4, using small interfering RNA reversed the suppressive effects of BMP15 on Cx43 expression and GJIC activity. The suppressive effects of BMP15 on Cx43 expression were further confirmed in primary human granulosa-lutein cells obtained from infertile patients undergoing an in vitro fertilization procedure. These findings suggest that oocyte-derived BMP15 decreases GJIC activity between human granulosa cells by down-regulating Cx43 expression, most likely via a Smad-dependent signaling pathway. KEYWORDS: BMP15, GDF9, connexin43, human granulosa cell, smad

PMID 24413384


Wnt signaling specifies and patterns intestinal endoderm

Mech Dev. 2011 Aug 10. [Epub ahead of print]

Sherwood RI, Maehr R, Mazzoni EO, Melton DA. SourceBrigham and Women's Hospital and Harvard Medical School, NRB Room 468, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.


Wnt signaling has been implicated in many developmental processes, but its role in early endoderm development is not well understood. Wnt signaling is active in posterior endoderm as early as E7.5. Genetic and chemical activation show that the Wnt pathway acts directly on endoderm to induce the intestinal master regulator Cdx2, shifting global gene away from anterior endoderm and toward a posterior, intestinal program. In a mouse embryonic stem cell differentiation platform that yields pure populations of definitive endoderm, Wnt signaling induces intestinal gene expression in all cells. We have identified a set of genes specific to the anterior small intestine, posterior small intestine, and large intestine during early development, and show that Wnt, through Cdx2, activates large intestinal gene expression at high doses and small intestinal gene expression at lower doses. These findings shed light on the mechanism of embryonic intestinal induction and provide a method to manipulate intestinal development from embryonic stem cells.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PMID 21854845


Wnt and TGF-beta signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells

Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16806-11. Epub 2006 Oct 31.

Gadue P, Huber TL, Paddison PJ, Keller GM. SourceDepartment of Gene and Cell Medicine, Black Family Stem Cell Institute, Mount Sinai School of Medicine, 1 Gustave Levy Place, Box 1496, New York, NY 10029, USA.


The establishment of the primitive streak and its derivative germ layers, mesoderm and endoderm, are prerequisite steps in the formation of many tissues. To model these developmental stages in vitro, an ES cell line was established that expresses CD4 from the foxa2 locus in addition to GFP from the brachyury locus. A GFP-Bry(+) population expressing variable levels of CD4-Foxa2 developed upon differentiation of this ES cell line. Analysis of gene-expression patterns and developmental potential revealed that the CD4-Foxa2(hi)GFP-Bry(+) population displays characteristics of the anterior primitive streak, whereas the CD4-Foxa2(lo)GFP-Bry(+) cells resemble the posterior streak. Using this model, we were able to demonstrate that Wnt and TGF-beta/nodal/activin signaling simultaneously were required for the generation of the CD4-Foxa2(+)GFP-Bry(+) population. Wnt or low levels of activin-induced a posterior primitive streak population, whereas high levels of activin resulted in an anterior streak fate. Finally, sustained activin signaling was found to stimulate endoderm commitment from the CD4-Foxa2(+)GFP-Bry(+) ES cell population. These findings demonstrate that the early developmental events involved in germ-layer induction in the embryo are recapitulated in the ES cell model and uncover insights into the signaling pathways involved in the establishment of mesoderm and endoderm.

PMID 17077151