Extramacrochaete promotes branch and bouton number via the sequestration of Daughterless in the cytoplasm of neurons.

Abstract

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 have shown that these proteins must homodimerize or heterodimerize with tissue specific HLH proteins in order to bind DNA at E box (CANNTG) consensus sequences to control tissue specific transcription. Due to its ubiquitous expression, class I bHLH proteins are also extensively regulated post-translationally, 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 Extramacrochaete 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 Extramacrochatae in neurons while providing a novel understanding of how Extramacrochaetae functions to restricts Daughterless activity within the cell.