Understanding the early development of sensory placodes and its underlying molecular and genetic control is essential for progress in the alleviation of genetic-determined sensory perception disorders and congenital diseases. Our long-term goal is to understand how cells are specified to form sensory organs. Investigations are proposed to study sensory placode formation in the relatively small and simple zebrafish embryo. This species has many attributes for both developmental and genetic studies, and can serve as model system for understanding the development of sensory organs in all vertebrates, including humans. The proposed experiments address the molecular requirements of sensory placode formation. Specifically: 1. The nature of the defects in early placode formation, caused by a mutation that leads to an apparent loss of otic and olfactory placodes will be examined. To date, no mutation in any vertebrate has been described that shows a complete loss of sensory placodes. The experiments will reveal whether the function(s) removed in this mutation lead to a complete absence of any placodal characteristics. 2. Two highly conserved transcription factors, dlx3 and dlx7, have been removed by this mutation. This analysis will test the prediction that these two genes are necessary to establish a region of competence to respond to inductive signals required for placode formation. Two learn whether dlx37 are necessary to form sensory placodes, we will isolate point mutations in these genes. The possible redundancy of these two genes in that process will be examined by providing wild type transgenes for either dlx3 or dlx7. 3. We will compare the expression patterns of dlx3/7 to that of other genes to adds the current model that placodes are ectodermal, rather than neuroectodermal, in origin. Understanding the developmental origin of placode primordia will lead to a better picture of the molecular requirements and interactions involved in their formation. 4. Molecular and genetic analyses will be used to find gene functions that regulate or are regulated by dlx3 and dlx7 to identify the molecular requirements for sensory placode development. This analysis will identify novel genes on the basis of their function in the initiation and formation of sensory placodes.
