POWRE: Interactions Among Hox10 Paralogous Genes During Nervous System Development

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

This project focuses on three genes, Hoxa10, Hoxc10, and Hoxd10, and examines their combined activity in the development of the nervous system. These three genes, which encode transcription regulators, are expressed at lumbar levels in the developing embryo and are thought to provide regional identity to the spinal cord and surrounding tissues. Because these genes are expressed in similar patterns and appear to regulate similar processes, they may interact directly with each other or may act in concert to regulate common downstream target genes. Using knockout mice, the current studies will address interactions between the three genes by characterizing alterations in spinal cord development at the cellular and molecular level. At the cellular level, spinal cord motor neurons will be examined for changes in identity and projection in double mutant animals. Observations in single mutant animals suggest that the development of this population of cells is regulated by several different Hox genes; combinatorial interactions between Hox genes may produce more dramatic alterations in motor neuron development. Molecular interactions will be identified using quantitative RT-PCR and downstream targets of gene activity will be identified using microarray assay screening. These studies will demonstrate that three Hox genes act in combination to regulate the cellular and molecular identity of the developing nervous system. Normal development of the spinal cord requires that the correct cells be produced in the proper place at the proper time in order to ensure the integrated functioning of the nervous system. Alterations in cell production can produce diseases such as spinal muscular atrophy or lethal congenital contracture syndrome. The studies to be conducted will examine how several genes may interact with each other to produce the unique cellular and molecular structure of the developing lumbar spinal cord. It is anticipated that this POWRE award will allow Dr. Carpenter's research to move forward more rapidly after a prolonged period of administrative responsibility and will permit the introduction of microarray technology into her laboratory.