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

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* '''A new developmental mechanism for the separation of the mammalian middle ear ossicles from the jaw'''<ref name ="PMID28179517"><pubmed>28179517</pubmed></ref> "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." [[Hearing - Middle Ear Development|Middle Ear Development]]
 
* '''Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases  gap junction intercellular communication (GJIC) activity in immortalized human granulosa cells'''<ref name ="PMID24413384"><pubmed>24413384</pubmed></ref> "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."
 
* '''Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases  gap junction intercellular communication (GJIC) activity in immortalized human granulosa cells'''<ref name ="PMID24413384"><pubmed>24413384</pubmed></ref> "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'''<ref name ="PMID23620745"><pubmed>23620745</pubmed></ref> "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]]
 
* '''Spatio-temporal distribution of Smads and role of Smads/TGF-β/BMP-4 in the regulation of mouse bladder organogenesis'''<ref name ="PMID23620745"><pubmed>23620745</pubmed></ref> "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]]

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Introduction

Transforming Growth Factor-beta (TGF-β) this singling pathway family has many different roles during development.

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

  • A new developmental mechanism for the separation of the mammalian middle ear ossicles from the jaw[2] "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." Middle Ear Development
  • Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases gap junction intercellular communication (GJIC) activity in immortalized human granulosa cells[3] "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[4] "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
More recent papers
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Search term: TGF-β Embryology

<pubmed limit=5>TGF-β Embryology</pubmed>

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

Implantation

Expressed at the fetal-maternal interface and implicated in the promotion of implantation and post-implantation development.[5]

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.

SMAD

SMAD5

Mothers against decapentaplegic homolog 5 (SMAD5) is a transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase.

OMIM: SMAD5

Bone morphogenetic protein 15

BMP15 evolution among family members.jpg

BMP15 evolution among family members[6]

Growth Differentiation Factor 9

Bovine ovarian follicle BMP15 and GDF9 expression[7]

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).[8][9][10]

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.[3]


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. <pubmed>28179517</pubmed>
  3. 3.0 3.1 <pubmed>24413384</pubmed>
  4. <pubmed>23620745</pubmed>
  5. <pubmed>16885531</pubmed>
  6. <pubmed>24147118</pubmed>| PLoS One.
  7. <pubmed>21401961</pubmed>| Reprod Biol Endocrinol.
  8. <pubmed>15454632</pubmed>
  9. <pubmed>5531364</pubmed>
  10. <pubmed>24313324</pubmed>

Reviews

Articles

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

Online Textbooks

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Cite this page: Hill, M.A. (2019, October 23) 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