As olfactory sensory neuron (OSN) axons approach the olfactory bulb (OB) they reorganize and coalesce into glomeruli homogeneous for odor receptor (OR) expression. ORs are necessary for OSN axon extension and convergence, but alternative mechanisms are also implicated.
Olfactory nerve development begins with the migration of cells into the mesenchyme from the olfactory placode (OP) and extension of OSN axons across the basal lamina. Chapter 2 tests the hypothesis that migration of OP cells into the mesenchyme precedes the emergence of OSN axons. We show molecularly distinct subpopulations of neurons emerging from the OP at ∼E10 to establish the migratory mass (MM) 24 hours prior to the appearance of the first few scattered OSN axon fascicles at ∼E11.
In Chapter 3 we show that the first OSN axons emerging from the OP into the MM segregate into molecularly defined sub-populations that will innervate delineated regions within the OB; in effect, that a regionally defined pre-target axon sorting occurs. While regional segregation is evident in the mesenchyme, convergence of OR-specific subpopulations does not occur until the axons reach the inner nerve layer of the OB, proximal to their final glomerular convergence. Thus, OSN axon organization is hierarchically organized.
We propose that the mesenchyme is a sorting zone for the regional topographic organization of the OSN axons. The precocious emigration of molecularly heterogeneous neurons into the mesenchyme contributes to the formation of a scaffold of guidepost cells we hypothesize are critical for the proper sorting of the OSN axons.
Chapter 4 explores in detail the role of the hyperpolarization activated current (Ih) in modulating activity-dependent mechanisms of OSN axon extension and coalescence. Chapter 5 explores further the role of the OR in axon extension by determining embryonic appearance of ORs and regulatory mechanisms of OR family member expression.
Collectively, the work reported here extends our understanding of the complex myriad of mechanisms that underlie the specificity of axon organization and coalescence in the olfactory pathway. The work also brings to light potential mechanisms that may be operative elsewhere during development of the nervous system, but have not yet been fully explored.
|School Location:||United States -- Connecticut|
|Source:||DAI-B 72/10, Dissertation Abstracts International|
|Subjects:||Neurosciences, Developmental biology|
|Keywords:||Axon guidance, Mesenchymal sorting zone, Migratory mass, Olfactory nerve|
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