Difference between revisions of "Developmental Signals - TGF-beta"

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* '''Smad1/5''' - associated with BMP-like signalling.
 
* '''Smad1/5''' - associated with BMP-like signalling.
 
* '''Smad2/3''' - associated with TGF-β-like signaling.
 
* '''Smad2/3''' - associated with TGF-β-like signaling.
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==Bone morphogenetic protein 15==
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[[File:BMP15_evolution_among_family_members.jpg|600px]]
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BMP15 evolution among family members<ref name=PMID24147118><pubmed>24147118</pubmed>| [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078199 PLoS One.]</ref>
  
 
==Growth Differentiation Factor 9==
 
==Growth Differentiation Factor 9==
[[File:BMP15_evolution_among_family_members.jpg|thumb|300px|BMP15 evolution among family members<ref name=PMID24147118><pubmed>24147118</pubmed>| [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078199 PLoS One.]</ref>]]
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[[File:Bovine ovarian follicle BMP15 and GDF9 expression.jpg|thumb|300px|BMP15 evolution among family members<ref name=PMID21401961><pubmed>21401961</pubmed>| [http://www.rbej.com/content/9/1/33 Reprod Biol Endocrinol.]</ref>]]
 
Growth Differentiation Factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are both members of the transforming growth factor-β (TGF-β) superfamily. They have both been identified as growth factors required oocyte to granulosa cell signaling for ovarian follicle development (folliculogenesis).<ref name=PMID15454632><pubmed>15454632</pubmed></ref><ref name=PMID5531364><pubmed>5531364</pubmed></ref><ref name=PMID24313324><pubmed>24313324</pubmed></ref>
 
Growth Differentiation Factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are both members of the transforming growth factor-β (TGF-β) superfamily. They have both been identified as growth factors required oocyte to granulosa cell signaling for ovarian follicle development (folliculogenesis).<ref name=PMID15454632><pubmed>15454632</pubmed></ref><ref name=PMID5531364><pubmed>5531364</pubmed></ref><ref name=PMID24313324><pubmed>24313324</pubmed></ref>
  

Revision as of 17:12, 10 February 2014

Introduction

Transforming Growth Factor-beta (TGF-β)

TGF-beta signaling pathway[1]


Factor Links: AMH | hCG | BMP | sonic hedgehog | bHLH | HOX | FGF | FOX | Hippo | LIM | Nanog | NGF | Nodal | Notch | PAX | retinoic acid | SIX | Slit2/Robo1 | SOX | TBX | TGF-beta | VEGF | WNT | Category:Molecular

Some Recent Findings

  • Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases gap junction intercellular communication (GJIC) activity in immortalized human granulosa cells[2] "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. ...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."
  • Spatio-temporal distribution of Smads and role of Smads/TGF-β/BMP-4 in the regulation of mouse bladder organogenesis[3] "Although Shh, TGF-β and BMP-4 regulate radial patterning of the bladder mesenchyme and smooth muscle differentiation, it is not known what transcription factors, local environmental cues or signaling cascades mediate bladder smooth muscle differentiation. ...Based on the Smad expression patterns, we suggest that individual or combinations of Smads may be necessary during mouse bladder organogenesis and may be critical mediators for bladder smooth muscle differentiation." Urinary Bladder Development

Structure

The TGF precursor protein has three distinct regions:

  1. signal peptide - targets it to the endoplasmic reticulum and secretion
  2. propeptide - or the latency associated peptide
  3. mature peptide - cleaved from the precursor protein and is actively involved in signalling
  • cleaved by Furin - a convertase
  • cleaved at a dibasic arginine-X-X-arginine (RXXR) site

Function

Signaling Pathway

TGF-beta signaling pathway[1]

Receptor

  1. active peptide forms a hetero- or homodimer
  2. binds to a specific TGF-β Type II receptor
  3. Type II receptor then recruits a TGF-β Type I receptor
  4. phosphorylates it via its serine/threonine kinase domain
  5. phosphorylated Type I receptors then phosphorylate receptor-associated Smad proteins (R-Smads), including Smad1/5 and Smad2/3
  • Type II receptor - MlTgfRII
  • Type I receptors - MlTgfRIa, MlTgfRIb, and MlTgfRIc

Intracellular Signaling

  • R-Smad proteins are composed of two main functional domains
    • Mad-homology domains 1 and 2 (MH1 and MH2)
  • Smad1/5 - associated with BMP-like signalling.
  • Smad2/3 - associated with TGF-β-like signaling.


Bone morphogenetic protein 15

BMP15 evolution among family members.jpg

BMP15 evolution among family members[4]

Growth Differentiation Factor 9

BMP15 evolution among family members[5]

Growth Differentiation Factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are both members of the transforming growth factor-β (TGF-β) superfamily. They have both been identified as growth factors required oocyte to granulosa cell signaling for ovarian follicle development (folliculogenesis).[6][7][8]

A recent study in pig has shown that oocyte-derived BMP15 but not GDF9 is required for down-regulation of connexin43 expression leading to a decrease in intercellular gap junction communication in granulosa cells.[2]


Links: TGF-beta | Bone Morphogenetic Protein | Oocyte Development | Ovary Development | Menstrual Cycle | OMIM - GDF9

OMIM

About OMIM "Online Mendelian Inheritance in Man OMIM is a comprehensive, authoritative, and timely compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries contain copious links to other genetics resources." OMIM


References

  1. 1.0 1.1 Pang K, Ryan JF, Baxevanis AD, Martindale MQ (2011) Evolution of the TGF-β Signaling Pathway and Its Potential Role in the Ctenophore, Mnemiopsis leidyi. PLoS ONE 6(9): e24152 PLoS ONE
  2. 2.0 2.1 <pubmed>24413384</pubmed>
  3. <pubmed>23620745</pubmed>
  4. <pubmed>24147118</pubmed>| PLoS One.
  5. <pubmed>21401961</pubmed>| Reprod Biol Endocrinol.
  6. <pubmed>15454632</pubmed>
  7. <pubmed>5531364</pubmed>
  8. <pubmed>24313324</pubmed>

Reviews

Articles

<pubmed>19192293</pubmed>| BMC Evol Biol. <pubmed>17077151</pubmed>

Online Textbooks

Search PubMed

External Links

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Cite this page: Hill, M.A. (2019, October 24) Embryology Developmental Signals - TGF-beta. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_TGF-beta

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G