Neurogenesis – the process of making new neurons – is indispensable for normal development and for adult homeostasis and repair. Many of the signalling and transcriptional events that regulate the specification and differentiation of neural progenitor cells (NPCs) into neurons have been uncovered; however, how these events are coordinated at a post-translational level is not well defined. Now, on p. 3085, Miho Matsuda, Ajay Chitnis and colleagues identify the protein Epb41l5 – an adaptor protein that links cytoplasmic proteins to specific membrane compartments – as a new regulator of neuronal differentiation in the developing zebrafish hindbrain. The authors first identify Epb41l5 in a yeast two-hybrid screen against Mib1, a key component of the Notch signalling pathway. Using Epb41l5-deficient embryos, the authors show that loss of Epb41l5 impairs neuronal differentiation, but that this can be partially rescued by knockdown of N-cadherin expression, suggesting a possible role for Epb41l5 in the disassembly of apical adherens junctions. In support of this, the authors further demonstrate that Mib binding to Epb41l5 facilitates its degradation and thus promotes apical adhesions, which may impair proper delamination and differentiation. The authors conclude by proposing a model whereby changes in Notch ligand levels that occur during neuronal differentiation protect Epb41l5 from Mib1-mediated degradation, thereby facilitating neuroepithelial detachment and subsequent differentiation.
- © 2016. Published by The Company of Biologists Ltd