Cellular and molecular mechanisms regulating embryonic neurogenesis in the rodent olfactory epithelium

Mechanisms that regulate cellular differentiation in developing embryos are maintained across multiple physiological systems, including the nervous system where neurons and glia are generated. The olfactory epithelium, which arises from the olfactory pit, is a stratified tissue in which the stepwise generation of neurons and support cells can easily be assessed and followed during embryogenesis and throughout adulthood. During olfactory epithelium morphogenesis, progenitor cells respond to factors that control their proliferation, survival, and differentiation in order to generate olfactory receptor neurons that detect odorants in the environment and glia-like sustentacular cells. The tight temporal regulation of expression of proneural genes in dividing progenitor cells, including Mash-1, Neurogenin-1, and NeuroD1, plays a central role in the production of olfactory receptor neurons. Multiple factors that either positively or negatively affect the generation of olfactory receptor neurons have been identified and shown to impinge on the transcriptional regulatory network in dividing progenitor cells. Several growth factors, such as FGF-8, act to promote neurogenesis by ensuring survival of progenitor cells that will give rise to olfactory receptor neurons. In contrast, other molecules, including members of the large TGF-β family of proteins, have negative impacts on neurogenesis by restricting progenitor cell proliferation and stalling their differentiation. Since recent reviews have focused on neurogenesis in the regenerating adult olfactory epithelium, this review describes neurogenesis at embryonic stages of olfactory epithelium development and summarizes our current understanding of how both cell intrinsic and extrinsic factors control this process.