The goal of the Section on Developmental Neuroscience is to identify the cellular, molecular and genetic factors that play a role in the development of the sensory epithelium of the mammalian cochlea, the organ of Corti. The organ of Corti is comprised of a highly rigorous pattern of specialized cell types that has been shown to be required for normal hearing. During the last year, members of the laboratory concentrated on several different issues related to the development of the organ of Corti. Previous results from our laboratory and other laboratories had identified the basic helix-loop-helix transcription factor (bHLH) Math1 as a key regulator of the development of mechanosensory hair cells. However the specific role of Math1 has not been determined. In particular, while deletion of Math1 results in an absence of hair cells, it is not clear whether supporting cells, another important cell type within the organ of Corti, are also affected. To examine this possibility, cochleae were obtained from animals containing a targeted mutation in Math1. The presence of supporting cells in these cochleae was then analyzed using a combination of morphological and molecular techniques. Results indicated that development of supporting cells is significantly disrupted in Math1 mutants. To determine the specific effects of Math1, we generated an inducible form of Math1 that was then used to transiently express Math1 in the greater epithelial ridge, a population of epithelial cells within the cochlea that have been shown to be able to develop as hair cells under some circumstances. Transient activation of Math1 in these cells induced the formation of clusters of sensory epithelium that contained both hair cells and associated non-sensory supporting cells. However, while development of hair cells required expression of Math1, supporting cells could develop from either cells expressing Math1, or adjacent cells that did not express Math1. These results demonstrated inductive interactions between adjacent cells play a key role in regulating cell fate and the formation of the sensory epithelium within the cochlea. In a separate series of experiments we examined the role of cellular growth and rearrangement in the formation of cellular pattern within the organ of Corti of the cochlea. Development of the organ of Corti occurs in parallel with extension of the cochlear duct. To examine whether these two events might be linked, we determined the changes in cell size and number of cell contacts within the organ of Corti during the growth of the cochlear duct. Results indicated that the population of cells that will develop as the organ of Corti undergo a period of rearrangement in which the overall shape of the structure changes from short and wide to long and thin. This type of change in shape is referred to as convergence and extension and is consistent with a role for growth of the cochlear duct in the patterning of the organ of Corti.
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