Vertebrates have two pairs homologous of appendages, the forelimbs and the hindlimbs. Although these appendages are morphologically distinct, it appears that the genetic networks controlling their development act equivalently in both appendages. While the mechanisms that initiate limb outgrowth and its polarity establishment are reasonably well understood, much less is known about genes regulating limb identity specification. A single gene, the transcription factor Pitx1, has been clearly demonstrated to determine limb-type identity in mouse. Therefore, the transcriptional targets of Pitx1 are excellent candidates to be key of the genetic network leading limb identity determination. By combining mouse molecular genetic methods and microarray screening technologies, I aim to identify novel players of limb-identity determination. We propose to exploit Pitx1 null mouse to undertake a DNA microarray screen. The resulting candidate genes will then be verified, characterised and functionally assessed by complementary approaches using mouse and chick. This work will enhance our understanding of the genetics networks leading to limb-identity specification. More broadly, this project will increase our knowledge of how common signalling cascades acting in a population of progenitor cells are modulated to generate diverse structures.
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