Somitogenesis in the context of spondylocostal dysostosis (WP4785)

Homo sapiens

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Taken from The role of Notch in patterning the human vertebral column by Sally L Dunwoodie [https://www.ncbi.nlm.nih.gov/pubmed/19608404] and The many roles of Notch signaling during vertebrate somitogenesis by Kanu Wahi, Matthew S. Bochter, Susan E. Cole [https://www.ncbi.nlm.nih.gov/pubmed/25483003]. Spondylocostal dysostosis-associated genes refine Notch1 signaling in the anterior presomitic mesoderm in mammalian somitogenesis. Interaction between Notch pathway components. Dll1 activates Notch1 signaling producing N1ICD, and Dll3 inhibits Notch1 signaling. N1ICD activates transcription of Mesp2, Lfng and Hes7. Hes7 protein inhibits its own transcription and that of Lfng. The effect of Lfng on Notch1 signaling is contradictory; it can potentiate Notch1 signaling in cultured mammalian cells, and inhibit signaling in the embryo. Mesp2 protein activates the transcription of Lfng, Ripply2 and Epha4. Ripply2 inhibits the transcription of Mesp2 and Epha4 is implicated in somite border formation in zebrafish but is not required for this in mouse. Linked with a dotted arrow to the GeneProduct nodes are diseases caused by mutation in the respective gene.

Authors

Ritchie Lee , Kristina Hanspers , and Eric Weitz

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Skeletal Dysplasia

Annotations

Disease Ontology

spondylocostal dysostosis Adams-Oliver syndrome

Pathway Ontology

altered Notch signaling pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
DLL3 GeneProduct ensembl:ENSG00000090932
TBX6 GeneProduct ensembl:ENSG00000149922
EPHA4 GeneProduct ensembl:ENSG00000116106
LFNG GeneProduct ensembl:ENSG00000106003
RIPPLY2 GeneProduct ensembl:ENSG00000203877
HES7 GeneProduct ensembl:ENSG00000179111
DLL1 GeneProduct ensembl:ENSG00000198719
NOTCH1 GeneProduct ensembl:ENSG00000148400
MESP2 GeneProduct ensembl:ENSG00000188095

References

  1. Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm. Bessho Y, Miyoshi G, Sakata R, Kageyama R. Genes Cells. 2001 Feb;6(2):175–85. PubMed Europe PMC Scholia
  2. Periodic Lunatic fringe expression is controlled during segmentation by a cyclic transcriptional enhancer responsive to notch signaling. Morales AV, Yasuda Y, Ish-Horowicz D. Dev Cell. 2002 Jul;3(1):63–74. PubMed Europe PMC Scholia
  3. Clock regulatory elements control cyclic expression of Lunatic fringe during somitogenesis. Cole SE, Levorse JM, Tilghman SM, Vogt TF. Dev Cell. 2002 Jul;3(1):75–84. PubMed Europe PMC Scholia
  4. Periodic notch inhibition by lunatic fringe underlies the chick segmentation clock. Dale JK, Maroto M, Dequeant ML, Malapert P, McGrew M, Pourquie O. Nature. 2003 Jan 16;421(6920):275–8. PubMed Europe PMC Scholia
  5. Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by Delta1 and Jagged1. Yang LT, Nichols JT, Yao C, Manilay JO, Robey EA, Weinmaster G. Mol Biol Cell. 2005 Feb;16(2):927–42. PubMed Europe PMC Scholia
  6. The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity. Morimoto M, Takahashi Y, Endo M, Saga Y. Nature. 2005 May 19;435(7040):354–9. PubMed Europe PMC Scholia
  7. The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands. Ladi E, Nichols JT, Ge W, Miyamoto A, Yao C, Yang LT, et al. J Cell Biol. 2005 Sep 12;170(6):983–92. PubMed Europe PMC Scholia
  8. Negative feedback loop formed by Lunatic fringe and Hes7 controls their oscillatory expression during somitogenesis. Chen J, Kang L, Zhang N. Genesis. 2005 Dec;43(4):196–204. PubMed Europe PMC Scholia
  9. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression. Yasuhiko Y, Haraguchi S, Kitajima S, Takahashi Y, Kanno J, Saga Y. Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3651–6. PubMed Europe PMC Scholia
  10. Identification of Epha4 enhancer required for segmental expression and the regulation by Mesp2. Nakajima Y, Morimoto M, Takahashi Y, Koseki H, Saga Y. Development. 2006 Jul;133(13):2517–25. PubMed Europe PMC Scholia
  11. The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite. Morimoto M, Sasaki N, Oginuma M, Kiso M, Igarashi K, Aizaki K ichi, et al. Development. 2007 Apr;134(8):1561–9. PubMed Europe PMC Scholia
  12. Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome. Cornier AS, Staehling-Hampton K, Delventhal KM, Saga Y, Caubet JF, Sasaki N, et al. Am J Hum Genet. 2008 Jun;82(6):1334–41. PubMed Europe PMC Scholia
  13. Mesp2 and Tbx6 cooperatively create periodic patterns coupled with the clock machinery during mouse somitogenesis. Oginuma M, Niwa Y, Chapman DL, Saga Y. Development. 2008 Aug;135(15):2555–62. PubMed Europe PMC Scholia
  14. Functional importance of evolutionally conserved Tbx6 binding sites in the presomitic mesoderm-specific enhancer of Mesp2. Yasuhiko Y, Kitajima S, Takahashi Y, Oginuma M, Kagiwada H, Kanno J, et al. Development. 2008 Nov;135(21):3511–9. PubMed Europe PMC Scholia
  15. The role of Notch in patterning the human vertebral column. Dunwoodie SL. Curr Opin Genet Dev. 2009 Aug;19(4):329–37. PubMed Europe PMC Scholia
  16. The many roles of Notch signaling during vertebrate somitogenesis. Wahi K, Bochter MS, Cole SE. Semin Cell Dev Biol. 2016 Jan;49:68–75. PubMed Europe PMC Scholia
  17. Ripply2 recruits proteasome complex for Tbx6 degradation to define segment border during murine somitogenesis. Zhao W, Oginuma M, Ajima R, Kiso M, Okubo A, Saga Y. Elife. 2018 May 15;7:e33068. PubMed Europe PMC Scholia