Extramacrochaetae promotes branch and bouton number via the sequestration of daughterless in the cytoplasm of neurons

• Published in: Developmental neurobiology (Hoboken, N.J.) N.J.), 2019-08, Vol.79 (8), p.805-818
• Main Authors: Waddell, Edward A., Viveiros, Jennifer M., Robinson, Erin L., Sharoni, Michal A., Latcheva, Nina K., Marenda, Daniel R.
• Format: Article
• Language: English
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; bHLH; Cell Proliferation - physiology; Cytoplasm; Cytoplasm - metabolism; daughterless; Deoxyribonucleic acid; Dimerization; DNA; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Emc; Gene Expression Regulation, Developmental - genetics; Helix-loop-helix proteins (basic); HLH; Neurogenesis; Neurogenesis - physiology; Neurons; Neurons - metabolism; NMJ; Nucleotide sequence; Pitt–Hopkins; Presynaptic Terminals - metabolism; proneural; Proteins; Repressor Proteins - genetics; Repressor Proteins - metabolism; schizophrenia; Synapses; Tcf4; Transcription factors
• ISSN: 1932-8451; 1932-846X
• DOI: 10.1002/dneu.22720

The Class I basic helix–loop–helix (bHLH) proteins are highly conserved transcription factors that are ubiquitously expressed. A wealth of literature on Class I bHLH proteins has shown that these proteins must homodimerize or heterodimerize with tissue‐specific HLH proteins in order to bind DNA at E‐box consensus sequences to control tissue‐specific transcription. Due to its ubiquitous expression, Class I bHLH proteins are also extensively regulated posttranslationally, mostly through dimerization. Previously, we reported that in addition to its role in promoting neurogenesis, the Class I bHLH protein daughterless also functions in mature neurons to restrict axon branching and synapse number. Here, we show that part of the molecular logic that specifies how daughterless functions in neurogenesis is also conserved in neurons. We show that the Type V HLH protein extramacrochaetae (Emc) binds to and represses daughterless function by sequestering daughterless to the cytoplasm. This work provides initial insights into the mechanisms underlying the function of daughterless and Emc in neurons while providing a novel understanding of how Emc functions to restrict daughterless activity within the cell.