Building the Olfactory System: Morphogenesis and Stem Cell Specification in the Olfactory Epithelium and Olfactory Bulb

Abstract Olfactory system development is essential for vertebrates to recognize edible food, distinguish conspecifics or benign species from competitors or predators, and reproduce successfully. The mechanisms that underlie the development of this sensory system are remarkably similar to those that mediate differentiation of bilaterally symmetric appendages that emerge from the vertebrate midline during embryogenesis: the limbs, the face and jaws, and aortic arches of the heart. Thus, olfactory morphogenesis – for both peripheral and central nervous system components – engages signaling pathways and transcriptional regulators that influence the development of appendages that are key either for interaction with the environment (limbs, jaw, and face), or homeostasis and survival (aortic arches). Subsequent differentiation of the olfactory pathway as a neural rather than musculo-skeletal or vascular structure reflects local modifications of signaling that leads to specification of distinct olfactory epithelial (OE) stem and progenitor cell populations, as well as parallel specification of forebrain structures that receive and process peripheral olfactory sensory information. The functions of some molecular regulators, and consequences of mutations in key genes, are similar to those seen in the limb, the face, and the heart. Others may be unique to the developing olfactory pathway or deployed in a quantitatively distinctive fashion. The concerted action of these genes results in coordinated development of peripheral olfactory receptor neurons and target regions in the central nervous system that represent, relay, and process olfactory information.