Migratory and Differentiation Mechanisms Coordinate Olfactory Neurogenesis

Neurogenesis requires the coordination of many processes including cell spatial patterning and differentiation. How these parts integrate to ensure proper organ assembly and function is challenging to understand in vivo, especially given the stochastic nature of vertebrate development. Here, I leverage imaging of the developing zebrafish olfactory epithelium to quantitatively investigate mechanisms of cellular spatial patterning and differentiation. I found that precursors thought to be derived from migratory neural crest cells exhibited different movement characteristics as compared to local, placode-derived precursors. Despite this, both neuronal precursor types displaced such that the cells tended to condense toward an apical-basal midline within the tissue, pointing to a radial, convergence-like coordination. Next, I investigated how Notch signaling and the transcription factor insm1a manifest their mutual antagonism and control of olfactory neurogenesis. Groups of contacting cells with reciprocal expression assemble in a lateral inhibition-like pattern in the basal olfactory epithelium. These ‘Neighborhoods’ express higher levels of the proneural gene neurod4 than other basal cells and are preferentially regulated by the morphogen retinoic acid, which has a pro-neurogenic effect and likely diffuses from the adjacent developing eye. Together, these data indicate an interorgan signaling axis that regulates neurodevelopment in vivo.