Conserved mechanisms appear to be responsible for the control of neural development in vertebrates and invertebrates. The atonal (ato) gene is an important regulatory switch for chordotonal organ formation in the peripheral nervous system (body wall, joints, auditory structures) of Drosophila. Several vertebrate homologues of ato have been described. The mouse Math1 gene shares the highest homology with ato when compared to the other mouse homologues. Expression studies have shown a striking conservation of the expression pattern between ato and Math1 in the two species: both genes are expressed in mechanotransducing organs of the body wall, joints, and auditory system. However, Math1 has also been shown t be expressed and required for the external granular layer of the cerebellum. No expression has been demonstrated for ato in the mid brain of Drosophila. I have shown that ato is indeed expressed in the fly CNS, and identified a CNS specific enhanced for ato. In addition, in collaboration with Dr. Huda Zoghbi's and Dr. Ruth Anne Eatock's labs, we have demonstrated a function for Math1 in the vertebrate ear. Thus the conservation between the two genes is not only structural, but also functional in developmental terms. i am proposing experiments to analyze the function of ato and Math1 in the tissues where their functions are not understood: the fly brain and the mouse inner ear. These studies will utilize the powerful genetics of Drosophila and the wealth of embryological analysis in the mouse inner ear, as well as techniques for histology and molecular biology to address the questions proposed, Understanding the mechanisms of neural development is important for understanding the pathologies that may result from perturbing normal development, as well as for designing effective treatment.
