HOX10 GENES REGULATE LUMBAR SPINAL CORD PATTERNING

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DESCRIPTION (Adapted from applicant's description): The experiments described in this proposal are designed to examine the role of a set of three paralogous Hox genes in patterning the developing lumbar spinal cord. These genes, Hoxa10, Hoxc10, and Hoxd10 are expressed in broad domains encompassing the lumbar spinal cord and were chosen for analysis because they are a complete paralogous group and together are likely to provide all of the patterning information dictated by this spatial location within the Hox complex. Three specific aims will be addressed: 1) to define the regional and local patterns of expression of Hoxa10, Hoxc10, and Hoxd10 in the developing lumbar spinal cord, 2) to identify the populations of cells in the lumbar spinal cord which express Hoxca10, Hoxc10, or Hoxd10, and 3) to demonstrate that inactivation of Hoxa10, Hoxc10, or Hoxd10 alters the production and placement of specific cell populations in the lumbar spinal cord. These experiments will test the hypothesis that the expression and activity of genes which regulate transcription, such as Hox genes, establish the regional and cellular identity of the developing central nervous system.