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The mouse notches up another success: understanding the causes of human vertebral malformation

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Abstract

The defining characteristic of all vertebrates is a spine composed of a regular sequence of vertebrae. In humans, congenital spinal defects occur with an incidence of 0.5–1 per 1,000 live births and arise when the formation of vertebral precursors in the embryo is disrupted. These precursors (somites) form in a process (somitogenesis) in which each somite is progressively separated from an unsegmented precursor tissue. In the past decade the underlying genetic mechanisms driving this complex process have been dissected using animal models, revealing that it requires the coordinated action of at least 300 genes. Deletion of many of these genes in the mouse produces phenotypes with similar vertebral defects to those observed in human congenital abnormalities. This review highlights the role that such mouse models have played in the identification of the genetic causes of the malsegmentation syndrome spondylocostal dysostosis.

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Acknowledgments

The research reported from our laboratory was performed with the support of project grants from the National Health and Medical Research Council (NHMRC: 142006, 404804, 635500) and the Australian Research Council (DP1094119); and research fellowships to SLD (Pfizer Foundation Australia and NHMRC 514900), GC (NHMRC 158043 and Cancer Institute of NSW 06/ECF/1-03), and DBS (Westfield-Belconnen Group).

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  1. Developmental Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2033, Australia

    Duncan B. Sparrow, Gavin Chapman & Sally L. Dunwoodie

  2. St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Kensington, NSW, 2033, Australia

    Duncan B. Sparrow, Gavin Chapman & Sally L. Dunwoodie

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  1. Duncan B. Sparrow
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  2. Gavin Chapman
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Correspondence to Sally L. Dunwoodie.

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Sparrow, D.B., Chapman, G. & Dunwoodie, S.L. The mouse notches up another success: understanding the causes of human vertebral malformation. Mamm Genome 22, 362–376 (2011). https://doi.org/10.1007/s00335-011-9335-5

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