Preface

Olfactory development has long been a cornerstone of developmental neurobiology. R. Y. Cajal's remarkable and perceptive observations on cellular organization and connectivity in the neonatal mammalian olfactory system helped him formulate his ideas on synapse and neuron doctrine. Recently, much interest has focused on development of the olfactory system, both to understand its neural foundation and for the valuable clues that these studies may provide for understanding neural development in general. Olfaction shares many common mechanisms of sensory development with other sensory systems, including neuronal proliferation, developmental cell death, cell lineage arid sorting, neuronal/glial differentiation and maturation, axon growth and guidance, target selection and synapse formation, functional synaptic stability and specialization. Moreover, olfaction shows many unique features that present valuable models and challenging research problems for today's developmental neurobiologist. Olfactory structures and pathways show unique homologies among vertebrate and invertebrate species. Olfaction is the earliest distant sense to develop during phylogenesis and ontogenesis and appears to be functional in the young of animals, even at the most rudimentary stages of development, aiding them in vital activities: the search for food; parental, sibling and conspecific recognition; and avoidance of danger. In altricial mammals, where the newborn has immature vision and audition, olfaction is critical for nipple search and suckling behavior, which ensure proper growth and survival. Even the olfactory system oJ the human fetus and newborn is precocious and responsive to maternal and food odorants, as judged by motor and facial responses of babies. The embryonic olfactory placodes give rise not only to olfactory receptor neurons (ORNs) but also to other neuronal cell types such as the LHRH neurons of the hypothalamus, which regulate reproduction in diverse species. The earliest ORNs to arise in the embryo may exert profound inductive influences on vertebrate forebrain including formation and differentiation of olfactory bulb (OB) neurons. In mammalian OB, the bulk of inhibitory periglomerular and granular interneurons arise postnatally, traversing along specific migratory paths from lateral ventricles to their final destination. Their arrival and functional activity endows the OB's main relay elements with improved integrative abilities. At a very different front, thanks to molecular neurobiologists such as Richard Axel and Linda Buck, it has been shown that no less than 1% of the genome is expressed in the population of ORNs. These genes encode for nearly 1000 types of protein, presumed to be the odorant receptors since their molecular structures closely resemble the transmembrane receptor proteins. Each receptor neuron is thought to express only one of these proteins, and all the ORNs expressing the same presumptive receptor protein converge their axons upon the same glomerulus (or glomerular cluster) in the OB. The developmental aspects of these findings are not known. Thanks to P. P. C. Graziadei and others, it is known that the ORNs are uniquely able to replace themselves in the adult animal, by recapitulating development over numerous cycles during lifetime. Upon severance of their axons or by chemical toxicant injury to their ciliated dendrites or by aging, O RNs undergo complete degeneration, only to be replaced by development of immature resting progenitors. These form a completely new receptor cell whose axon innervates the OB and reestablishes new functional connections. Notwithstanding these remarkable and significant properties of olfactory development and regeneration, collected studies on cellular and molecular aspects of olfactory development and regeneration have not appeared previously, perhaps owing to the relative paucity of such studies in the past. This collection of original research papers by internationally recognized investigators attempts to bridge this gap by focusing on cellular and molecular aspects of olfactory development and regeneration. Of the sixteen papers herein, seven are on olfactory epithelium, seven on vertebrate OB and two on the insect olfactory system. Utilizing molecular biological approaches such as co-expression ot ~" LacZ and olfactory marker protein (OMP) in transgenic mice, Walter et al. from Frank Margolis' laboratory at the University of Maryland, explore the roles of olfactory-specific proteins such as O MP during normal development and in regeneration. Another molecular biological contribution by Salehi-Ashtiani and Farbman from Albert Farbman's laboratory at Northwestern University