Fig. 5. A model of the regulatory interactions involved in the determination and differentiation of the olfactory sensory neuron lineage. Mash1 is expressed in both apical and basal progenitors in the OE. Apical progenitors are primary neuroepithelial cells that give rise to secondary progenitors that settle basally. Mash1, which is required for the expression of the Notch signalling genes Serrate 1 and Hes1 in apical progenitors, and for the generation of basal progenitors, has the characteristics of a determination gene in the OE. A number of genes encoding transcriptional regulators are activated downstream of Mash1 in basal progenitors, including Ngn1. Ngn1 function is required for expression of the neuronal differentiation gene NeuroD and the neuronal subtype determinant Phd1 and for differentiation of olfactory sensory neurons. In the absence of Ngn1, however, basal progenitors express the Notch signalling genes Ser2, Dll3 and Hes5 and the transcriptional regulators Ebf1 and Lhx2. Ngn1 is therefore required to initiate one of several parallel programs of OSN differentiation activated downstream of Mash1 in basal progenitors. Note that the pathway depicted in this figure only operates in a subset of OE progenitors (e.g. most progenitors at E12.5; see Discussion).
