Abstract
Author SummaryEarly during development, cells differentiate and take on specialized forms and functions. This requires the activation of specific genes for different cellular pathways. Our study addresses how this activation is regulated in the developing Drosophila nervous system. In this model, it is well known that proneural transcription factors are involved in directing cells to differentiate into various types of neurons. However, the mechanism by which they choreograph the activation of genes for neuronal differentiation is not clear. In this study, we focused on events leading to differentiation of mechanosensory neurons, which have specialized dendritic processes that mediate sensory perception. In these developing neurons we profiled the time course of gene expression that is triggered by the proneural factor atonal. Our analysis revealed the activation of genes required for the formation of these specialized dendrites, called cilia. We then identified several ways in which atonal regulated these genes. First, it activates intermediate transcription factors that regulate different subsets of differentiation genes. Second, in at least one case, atonal activates a differentiation gene directly, one that is involved in the formation of cilia (ciliogenesis). These findings offer new insight into how proneural factors regulate specialized neuronal differentiation pathways.
Highlights
Once an embryonic cell is committed to a particular fate, it is likely that a precisely ordered progression of gene expression is required to coordinate the complex cell biological events that eventually lead to its terminal differentiation
Our study addresses how this activation is regulated in the developing Drosophila nervous system
In these developing neurons we profiled the time course of gene expression that is triggered by the proneural factor atonal
Summary
Once an embryonic cell is committed to a particular fate, it is likely that a precisely ordered progression of gene expression is required to coordinate the complex cell biological events that eventually lead to its terminal differentiation. Determining how this progression is regulated is an important step towards understanding how cells acquire specialised morphologies and functions. Atonal (ato)-related proneural genes are required for neurogenesis in the spinal cord and cortex (neurogenin), cerebellum (atoh1), and retina (atoh7) [1]. Atoh is required for the formation of mechanosensory cells in the inner ear and in skin [2,3]. Whilst proneural genes are intensively studied, little is known of how their function leads to specific programs of neuronal differentiation
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