Talk:Developmental Signals - TGF-beta

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Cite this page: Hill, M.A. (2024, March 28) Embryology Developmental Signals - TGF-beta. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Developmental_Signals_-_TGF-beta

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Growth differentiation factor 9

<pubmed limit=5>Growth differentiation factor 9</pubmed>

2014

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

2011

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.

Abstract

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

2006

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.

Abstract

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