Abnormal vertebral segmentation and the notch signaling pathway in man

Peter D. Turnpenny, Ben Alman, Alberto S. Cornier, Philip F. Giampietro, Amaka Offiah, Olivier Tassy, Olivier Pourquié, Kenro Kusumi, Sally Dunwoodie

Research output: Contribution to journalReview articlepeer-review

116 Scopus citations


Abnormal vertebral segmentation (AVS) in man is a relatively common congenital malformation but cannot be subjected to the scientific analysis that is applied in animal models. Nevertheless, some spectacular advances in the cell biology and molecular genetics of somitogenesis in animal models have proved to be directly relevant to human disease. Some advances in our understanding have come through DNA linkage analysis in families demonstrating a clustering of AVS cases, as well as adopting a candidate gene approach. Only rarely do AVS phenotypes follow clear Mendelian inheritance, but three genes - DLL3, MESP2, and LNFG - have now been identified for spondylocostal dysostosis (SCD). SCD is characterized by extensive hemivertebrae, trunkal shortening, and abnormally aligned ribs with points of fusion. In familial cases clearly following a Mendelian pattern, autosomal recessive inheritance is more common than autosomal dominant and the genes identified are functional within the Notch signaling pathway. Other genes within the pathway cause diverse phenotypes such as Alagille syndrome (AGS) and CADASIL, conditions that may have their origin in defective vasculogenesis. Here, we deal mainly with SCD and AGS, and present a new classification system for AVS phenotypes, for which, hitherto, the terminology has been inconsistent and confusing.

Original languageEnglish (US)
Pages (from-to)1456-1474
Number of pages19
JournalDevelopmental Dynamics
Issue number6
StatePublished - Jun 2007


  • Abnormal vertebral segmentation
  • Alagille syndrome
  • DLL3
  • LNFG
  • MESP2
  • Notch signaling pathway
  • Spondylocostal dysostosis

ASJC Scopus subject areas

  • Developmental Biology


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