PgmNr D1456: Novel function of the class I bHLH protein Daughterless in postmitotic neurons.

Authors:
E. A. Waddell 1 ; E. L. Robinson 1 ; M. D'Rozario 1,2 ; D. R. Marenda 1,3


Institutes
1) Drexel University, Philadelphia, PA; 2) Washington University School of Medicine, St. Louis, MO; 3) Drexel University College of Medicine, Philadelphia, PA.


Keyword: core promoters and general transcription factors

Abstract:

Class I basic Helix Loop Helix (bHLH) proneural proteins are highly conserved transcription factors. Class I bHLH proteins are broadly expressed in multiple tissues and have critical roles in many developmental processes such as neurogenesis. However, little is known about how class I bHLH proteins function in mature, differentiated neurons. Class I bHLH proteins function during development by forming heterodimers with class II bHLH proteins to activate transcription or by forming homodimers to both activate or restrict transcription of target genes. Class I bHLH proteins can also heterodimerize with class V HLH proteins, preventing gene expression. Our laboratory has identified a novel role for the class I bHLH protein Daughterless (Da), the only class I bHLH protein in Drosophila. Neuromuscular junction dissections were performed on third instar larvae and mature motor neuron synapses were imaged from this tissue. We have shown that Da functions to restrict synaptic branching and synapse number in these postmitotic neurons. Furthermore, our laboratory has shown that Da accomplishes this in part through restricting the expression of Neurexin, a cell adhesion molecule required for synapse formation. Third instar larvae were dissected and direct immunohistochemistry was performed for α-Nrx1 to show Neurexin levels in Da knockdown and overexpression genotypes. The mammalian ortholog of Da, Transcription Factor 4 (TCF4), is a well-identified risk factor for a number of neurodevelopmental disorders including Pitt-Hopkins syndrome and schizophrenia, both of which are characterized by defects in behavior, learning, and memory. It is hypothesized that defects in postmitotic neurons may contribute to the phenotypes associated with these neurodevelopmental disorders. Therefore, identifying how Da functions to restrict synaptic branching and synapse number in postmitotic neurons will have a significant impact on our understanding of the etiology of these diseases.



Flybase Genetic Index:
1. FlyBase gene symbol: da; FBgn: FBgn0267821