Graham, Anthony; (1990) Analysis of murine homeobox genes. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The work in this thesis is consistent with, and strengthens, suggestions that murine homeobox genes play a role in the establishment of regional specification. It is shown that there is a correlation between the physical order of members of the Hox 2 cluster and their order of expression along the rostrocaudal axis, such that each more 3' gene is expressed more rostrally. Such a correlation has been previously shown for the Drosophila homeotic genes of the ANT-C and BX-C, where it was clear that these genes were involved in the establishment of regional identity along the rostrocaudal axis. It has also been demonstrated that the relationship between the murine and Drosophila clusters extends further than aspects of their expression patterns. Sequence comparisons suggest that the murine Hox clusters and the Drosophila homeobox clusters arose from a common ancestral cluster that existed prior to the divergence between the protostomes and the deuterostomes Therefore the corresponding utilisation of ordered region specific expression of members of homeobox clusters in flies and mice together with their conservation would suggest that these genes are involved in the establishment of rostrocaudal regional specification in these organisms, and by inference in all other higher metazoans. It is also demonstrated that the Hox 2 genes show spatially and temporally dynamic patterns of expression in the transverse plane of the developing central nervous system. Since all of the Hox 2 genes exhibit similar expression patterns it is felt they are reflecting events during ontogeny of the spinal cord. The observed patterns correlate with the timing and location of the birth of the major classes of neurons. It is suggested that the Hox 2 genes are conferring rostrocaudal positional information on each class of newly born neurons. These genes also exhibit a striking dorsal restriction in their expression within the developing spinal cord which does not appear to correlate with morphology and eventually breaks down.

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