Bickley, SRB; (2013) The Gene Tbx5 Links Development, Evolution and Adaptation of the Sternum in Terrestrial Vertebrates. Doctoral thesis , UCL (University College London).

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Abstract

The transition from fins to limbs during the colonisation of land was a key innovation in vertebrate evolution. Changes in the limb and shoulder girdle during this event have been investigated extensively, but little attention has been given to the acquisition of the sternum, a feature considered characteristic of virtually all terrestrial vertebrates, and which is mandatory for tetrapod locomotion. The sternum is a thin flat bone lying at the ventral midline of the thorax that provides a crucial attachment site for the pectoral muscles, allowing the forelimbs to raise the body up from the ground. I demonstrate that a sternum completely fails to form in conditional Tbx5 mutant mouse embryos. Consistent with this, sternum defects are a characteristic feature of Holt-Oram syndrome, which is caused by mutations in TBX5. While the role of Tbx5 in the development of the heart and forelimbs has been studied extensively, Tbx5 function in sternum formation is not understood. Using chick and mouse models systems, I set out to investigate the developmental origin of the sternum, and why it fails to form in the absence of Tbx5. Since the function of the sternum is to facilitate forelimb movement, I explored the correlation between forelimb use and sternum morphology by comparing sternum size across different avian species. I then investigated the genetic adaptations that could explain sternum and forelimb reduction in flightless birds, using the emu as a model. I suggest that Tbx5 represents a common node in the molecular pathways regulating forelimb and sternum development.

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