The Zinc-BED Transcription Factor Bedwarfed Promotes Proportional Dendritic Growth and Branching through Transcriptional and Translational Regulation in Drosophila

Abstract

Dendrites are the primary points of sensory or synaptic input to a neuron and play an essential role in synaptic integration and neural function. Despite the functional importance of dendrites, relatively less is known about the underlying mechanisms regulating cell type-specific dendritic patterning. Herein, we have dissected the functional roles of a previously uncharacterized gene, CG3995, in cell type-specific dendritic development in Drosophila melanogaster. CG3995, which we have named bedwarfed (bdwf), encodes a zinc-finger BED-type protein that is required for proportional growth and branching of dendritic arbors. It also exhibits nucleocytoplasmic expression and functions in both transcriptional and translational cellular pathways. At the transcriptional level, we demonstrate a reciprocal regulatory relationship between Bdwf and the homeodomain transcription factor (TF) Cut. We show that Cut positively regulates Bdwf expression and that Bdwf acts as a downstream effector of Cut-mediated dendritic development, whereas overexpression of Bdwf negatively regulates Cut expression in multidendritic sensory neurons. Proteomic analyses revealed that Bdwf interacts with ribosomal proteins and disruption of these proteins resulted in phenotypically similar dendritic hypotrophy defects as observed in bdwf mutant neurons. We further demonstrate that Bdwf and its ribosomal protein interactors are required for normal microtubule and F-actin cytoskeletal architecture. Finally, our findings reveal that Bdwf is required to promote protein translation and ribosome trafficking along the dendritic arbor. These findings shed light on the complex, combinatorial, and multi-functional roles of transcription factors (TFs) in directing the diversification of cell type-specific dendritic development.

Local Microtubule and F-Actin Distributions Fully Constrain the Spatial Geometry of Drosophila Sensory Dendritic Arbors

“…The transcription factor cut promotes F-actin dynamics by exerting combinatorial regulation through downstream effector molecules [ 14 ]. Cut positively regulates bdwf expression, which encodes a protein that regulates proportional growth and branching of dendritic arbors [ 30 ]. Overexpression of bdwf in turn downregulates cut expression in da neurons.…”

“…The ribosomal proteins RpS24 , RpL4 , RpL22, and RpL31 are physical interactors of bdwf . Similar to bdwf-IR , knockdown of any of these four proteins leads to a reduction in dendritic complexity, as well as a reduction in average cytoskeletal distributions [ 30 ]. Another downstream effector molecule of cut -mediated transcriptional regulation is PP2A phosphatase.…”