Neuronal regeneration: lessons from the olfactory system.

seminars in C E L L & D E V E L OP M E N T A L B I OL OG Y , Vol 10, 1999: pp. 421]431 Article No. scdb.1999.0329, available online at http:rrwww.idealibrary.com on Neuronal regeneration: Lessons from the olfactory system Richard C. Murray and Anne L. Calof Neuronal regeneration takes place in the primary relay of the olfactory system, the olfactory epithelium ( OE ) ; however, its synaptic target in the central nervous system, the olfactory bulb ( OB ) , undergoes continual neurogenesis but not true regeneration. In this review, cell interactions and growth factors regulating neurogenesis in both OE and OB are discussed. In addition, regulation of regeneration in the OE and regulation of neurogenesis in the OB are compared, with the goal of identifying characteristics that may account for the different abilities of these two tissues to regenerate. offering hope that, by learning how proliferation and differentiation of progenitor cells is regulated, it may be possible to identify conditions that promote frank neuronal regeneration in the CNS. Such information would be of considerable medical, as well as scienti- fic, significance. Interestingly, true neuronal regeneration is known to occur in adult mammals in the primary relay of odor detection, the olfactory epithelium Ž OE . . The OE contains undifferentiated progenitor cells that generate new neurons throughout life. 3,4 While the cell bodies of these neurons, the olfactory receptor neurons Ž ORNs . , remain in the periphery, they send axons to the OB and their interactions with the bulb are important in regulating OE structure and func- tion. Because of its peripheral location, the OE is readily accessible for study, both in tissue culture and in living animals, and much is known about the cell interactions and molecular factors that regulate neu- rogenesis and neuron replacement in this tissue Ž re- viewed in refs 5,6 . . Several principles have emerged from such studies, especially with regard to the na- ture of the signals that initiate neurogenesis and cause it to halt. In this review, we highlight some of these principles and compare them with ideas emerg- ing from studies of neurogenesis in the OB. Our goal is to identify parallels in how these processes are regulated between the OE, a peripheral neural tissue, and the OB, which is in the CNS. Key words: growth factors r neurogenesis r neuronal progenitor cells r olfactory epithelium r olfactory bulb Q1999 Academic Press Introduction M ANY TISSUES IN adult mammals are able to regener- ate their characteristic differentiated cell types throughout life, but this does not take place in most of the central nervous system Ž CNS . . Indeed, the inability of the CNS to generate new neurons in order to replace those that have been lost is a formidable obstacle to recovery from neuronal da- mage caused by injury or neurodegenerative disease, rendering such insults to the CNS devastating in their impact. However, there are parts of the CNS where long-term production of neurons takes place. These are the hippocampus and olfactory bulb Ž OB . of the brain, which continue to add new neurons through- out life. 1,2 This ongoing neurogenesis requires that neuronal progenitor cells exist in the adult brain, Structure of the primary olfactory pathway The primary olfactory pathway consists of the OE and its CNS target tissue, the OB Ž Figure 1A . . w In addition to this main olfactory system, many vertebrates pos- sess a separate system for the detection of phero- mones called the vomeronasal system Ž reviewed in ref 7 . , which will not be discussed in this review. x Odor detection initiates in the OE, a sensory epithelium that lines the nasal cavity. The OE consists of three From the Department of Anatomy and Neurobiology and the Developmental Biology Center, 364 Med Surge II, University of California, Irvine, College of Medicine, Irvine, CA 92697-1275, USA. Address reprint requests to murrayr@uci.edu Q1999 Academic Press 1084-9521r 99 r 040421q 11 $30.00r 0