Somitogenesis in the context of spondylocostal dysostosis (WP4785)

Homo sapiens

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


Ritchie Lee , Kristina Hanspers , and Eric Weitz


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Homo sapiens


Skeletal Dysplasia


Disease Ontology

spondylocostal dysostosis Adams-Oliver syndrome

Pathway Ontology

altered Notch signaling pathway


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


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