Somitogenesis in the context of spondylocostal dysostosis (Homo sapiens)

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16, 1781, 675, 111423, 410131221115913DLL3RIPPLY2EPHA4MESP2NOTCH1TBX6HES7LFNGDLL1OMIM:609813Spondylocostal Dysostosis 3, Autosomal RecessiveOMIM:613686Spondylocostal Dysostosis 4, Autosomal RecessiveOMIM:122600Spondylocostal Dysostosis 5OMIM:277300Spondylocostal Dysostosis 1, Autosomal RecessiveOMIM:616566Spondylocostal Dysostosis 6, Autosomal RecessiveOMIM:616028Adams-Oliver Syndrome 5OMIM:608681Spondylocostal Dysostosis 2, Autosomal Recessive


Taken from The role of Notch in patterning the human vertebral column by Sally L Dunwoodie [1] and The many roles of Notch signaling during vertebrate somitogenesis by Kanu Wahi, Matthew S. Bochter, Susan E. Cole [2].

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.

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  1. Morales AV, Yasuda Y, Ish-Horowicz D; ''Periodic Lunatic fringe expression is controlled during segmentation by a cyclic transcriptional enhancer responsive to notch signaling.''; Dev Cell, 2002 PubMed Europe PMC
  2. Ladi E, Nichols JT, Ge W, Miyamoto A, Yao C, Yang LT, Boulter J, Sun YE, Kintner C, Weinmaster G; ''The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands.''; J Cell Biol, 2005 PubMed Europe PMC
  3. Yasuhiko Y, Haraguchi S, Kitajima S, Takahashi Y, Kanno J, Saga Y; ''Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression.''; Proc Natl Acad Sci U S A, 2006 PubMed Europe PMC
  4. Yasuhiko Y, Kitajima S, Takahashi Y, Oginuma M, Kagiwada H, Kanno J, Saga Y; ''Functional importance of evolutionally conserved Tbx6 binding sites in the presomitic mesoderm-specific enhancer of Mesp2.''; Development, 2008 PubMed Europe PMC
  5. Dale JK, Maroto M, Dequeant ML, Malapert P, McGrew M, Pourquie O; ''Periodic notch inhibition by lunatic fringe underlies the chick segmentation clock.''; Nature, 2003 PubMed Europe PMC
  6. Cole SE, Levorse JM, Tilghman SM, Vogt TF; ''Clock regulatory elements control cyclic expression of Lunatic fringe during somitogenesis.''; Dev Cell, 2002 PubMed Europe PMC
  7. Morimoto M, Sasaki N, Oginuma M, Kiso M, Igarashi K, Aizaki K, Kanno J, Saga Y; ''The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite.''; Development, 2007 PubMed Europe PMC
  8. Cornier AS, Staehling-Hampton K, Delventhal KM, Saga Y, Caubet JF, Sasaki N, Ellard S, Young E, Ramirez N, Carlo SE, Torres J, Emans JB, Turnpenny PD, Pourquié O; ''Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome.''; Am J Hum Genet, 2008 PubMed Europe PMC
  9. Oginuma M, Niwa Y, Chapman DL, Saga Y; ''Mesp2 and Tbx6 cooperatively create periodic patterns coupled with the clock machinery during mouse somitogenesis.''; Development, 2008 PubMed Europe PMC
  10. Yang LT, Nichols JT, Yao C, Manilay JO, Robey EA, Weinmaster G; ''Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by Delta1 and Jagged1.''; Mol Biol Cell, 2005 PubMed Europe PMC
  11. Morimoto M, Takahashi Y, Endo M, Saga Y; ''The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity.''; Nature, 2005 PubMed Europe PMC
  12. Nakajima Y, Morimoto M, Takahashi Y, Koseki H, Saga Y; ''Identification of Epha4 enhancer required for segmental expression and the regulation by Mesp2.''; Development, 2006 PubMed Europe PMC
  13. Bessho Y, Miyoshi G, Sakata R, Kageyama R; ''Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm.''; Genes Cells, 2001 PubMed Europe PMC
  14. Zhao W, Oginuma M, Ajima R, Kiso M, Okubo A, Saga Y; ''Ripply2 recruits proteasome complex for Tbx6 degradation to define segment border during murine somitogenesis.''; Elife, 2018 PubMed Europe PMC
  15. Chen J, Kang L, Zhang N; ''Negative feedback loop formed by Lunatic fringe and Hes7 controls their oscillatory expression during somitogenesis.''; Genesis, 2005 PubMed Europe PMC
  16. Dunwoodie SL; ''The role of Notch in patterning the human vertebral column.''; Curr Opin Genet Dev, 2009 PubMed Europe PMC
  17. Wahi K, Bochter MS, Cole SE; ''The many roles of Notch signaling during vertebrate somitogenesis.''; Semin Cell Dev Biol, 2016 PubMed Europe PMC


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109332view23:33, 13 March 2020KhanspersOntology Term : 'spondylocostal dysostosis' added !
108794view03:11, 30 January 2020RleeUpdated literature references.
108793view03:09, 30 January 2020RleeModified description
108792view03:02, 30 January 2020RleeModified description
108791view03:01, 30 January 2020RleeNew pathway

External references


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NameTypeDatabase referenceComment
DLL1GeneProductENSG00000198719 (Ensembl)
DLL3GeneProductENSG00000090932 (Ensembl)
EPHA4GeneProductENSG00000116106 (Ensembl)
HES7GeneProductENSG00000179111 (Ensembl)
LFNGGeneProductENSG00000106003 (Ensembl)
MESP2GeneProductENSG00000188095 (Ensembl)
NOTCH1GeneProductENSG00000148400 (Ensembl)
RIPPLY2GeneProductENSG00000203877 (Ensembl)
TBX6GeneProductENSG00000149922 (Ensembl)

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