. In the mammalian brain, the olfactory bulb is the only region that receives not only continuous infusion of neuronal progenitor cells from the brain, but also renewed input from the olfactory epithelium. The olfactory sensory neurons (OSNs) continuously regenerate throughout the life of the animal. The newly-generated OSNs project precisely to stereotypical positions in the olfactory bulb to maintain a sensory map. It has been thought that the olfactory system does not exhibit a critical period during development because of its unique, continuous regenerative capacity. Our recent results show that axonal targeting of the OSNs is sensitive to deprivation of neural activity and other perturbations during the first postnatal week in olfactory development, suggesting a critical period in OSN axon targeting. Our data further suggest that two separate developmental programs underlie the precise targeting of the OSNs before and after the critical period. The switch is accompanied by a prominent change in the patterns of gene expression. The objective of this application is to determine the molecular control of the critical period in olfactory system development. By combining genetic manipulation and transcriptome analyses, we have developed approaches that allow us to directly compare the developmental programs during early postnatal period and in adulthood. We have identified candidate genes and we will test their role in determining the axon dynamics during the critical period and their role in determining the timing of the critical period. These studies will provide mechanistic insights into axon pathfinding during OSN development and during adult neurogenesis.
. The establishment of precise neuronal connection during development is essential for the function of the nervous system. Repairing damaged neuron and neuronal processes, regenerating neurons and the proper integration of these neurons into the adult brain are important aspects in maintaining the function of the nervous system throughout life. In the mammalian species, the olfactory system is the only nervous system that continuously regenerates. Adult-born neurons project to precise brain targets. This study will determine the molecular mechanisms that control the plasticity of axon pathfinding during development and during regeneration in the mouse olfactory system. Knowledge gained from this study will provide essential insights into the developmental regulation of regenerating neurons and provide important information on how the critical window of neural development is controlled. This may lead to the reopening of the critical period in neural development and benefit regenerative medicine.
| Wu, Yunming; Ma, Limei; Duyck, Kyle et al. (2018) A Population of Navigator Neurons Is Essential for Olfactory Map Formation during the Critical Period. Neuron 100:1066-1082.e6 |
