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Defective Somitogenesis and Abnormal Vertebral Segmentation in Man

  • Chapter
Somitogenesis

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 638))

Abstract

In recent years molecular genetics has revolutionized the study of somitogenesis in developmental biology and advances that have taken place in animal models have been applied successfully to human disease. Abnormal segmentation in man is a relatively common birth defect and advances in understanding have come through the study of cases clustered in families using DNA linkage analysis and candidate gene approaches, the latter stemming directly from knowledge gained through the study of animal models. Only a minority of abnormal segmentation phenotypes, appear to follow Mendelian inheritance but three genes—DLL3, MESP2 and LNFG—have now been identified for spondylocostal dysostosis (SCD), a spinal malformation characterized by extensive hemivertebrae, trunkal shortening and abnormally aligned ribs with points of fusion. In affected families autosomal recessive inheritance is followed. These genes are all important components of 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. This review deals mainly with SCD, with some consideration of AGS. Significant future challenges lie in identifying causes of the many abnormal segmentation phenotypes in man but it is hoped that combined approaches in collaboration with developmental biologists will reap rewards.

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Authors and Affiliations

  1. Peninsula Medical School Clinical Genetics Department, Royal Devon & Exeter Hospital, Gladstone Road, Exeter, UK

    Peter D. Turnpenny

  2. Clinical Genetics Department, Royal Devon & Exeter Hospital, Gladstone Road, Exeter, EX1 2ED, UK

    Peter D. Turnpenny

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  1. Peter D. Turnpenny
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  1. University of Dundee, Dundee, Scotland

    Miguel Maroto PhD

  2. University of Exeter, Devon, England

    Neil V. Whittock PhD

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© 2008 Landes Bioscience and Springer Science+Business Media, LLC

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Turnpenny, P.D. (2008). Defective Somitogenesis and Abnormal Vertebral Segmentation in Man. In: Maroto, M., Whittock, N.V. (eds) Somitogenesis. Advances in Experimental Medicine and Biology, vol 638. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09606-3_9

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