Genetic factors that control superior olivary complex neuron migration and maturation

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

? DESCRIPTION (provided by applicant): The superior olivary complex (SOC) is a group of six nuclei situated in the brainstem that are important for localizing sound. The genetic pathways that control SOC neuron development are largely unknown. Our laboratory previously identified the homeobox transcription factor En1 as important for the development of a subset of SOC neurons. We provide preliminary evidence in this proposal demonstrating that En1 is involved in the terminal migration and survival of these neurons. Furthermore, deletion of En1 in SOC neurons abolishes expression of FoxP1, a forkhead box transcription factor important for neuronal development in other brain regions. This proposal has two specific aims. The first aim will examine the consequences of conditional FoxP1 deletion during embryonic and postnatal development on SOC neuron positioning, morphology and neurochemical phenotypes. The second aim will explore how deletion of En1 in SOC neurons affects expression of a variety of molecules important for neuronal migration. We propose to use conditional deletion strategies, fate-mapping techniques, histology and auditory testing to assess the effects of these manipulations. We anticipate that findings from these experiments will enhance our understanding of the complex developmental pathways that govern SOC neuron migration and maturation. In turn, this will provide insights into pathologies that lead to SOC malformations in humans.