Abstract:
In the framework of this study, a systematic and quantitative analysis of the neurogenic process and the integration of adult-born olfactory sensory neurons (OSNs) into the zebrafish olfactory epithelium (OE) was performed. In the postlarval zebrafish OE OSNs are generated from two distinct proliferation zones at the central and peripheral margin of the sensory tissue. Temporal birthdating, using the proliferation marker BrdU reveals centrifugal migration of newly generated cells from the inner proliferation zones located at the interlamellar curves (ILCs) and centripetal migration of cells from the peripheral neurogenic zone at the sensory / non-sensory (S/NS) border. In addition to radial migration a basal to apical ascend was observed over time. Neuronal progenitor cells expressing proneuronal genes indicative of different stages of cellular differentiation and neuronal maturation could be visualized at or close to mitotically active zones at the ILC and S/NS. Fate tracking of new born OSNs at different time points following BrdU incubation showed that OSNs are rather immobile during early differentiation steps and complete neuronal maturation before completing migration. Analysis of newly generated OSNs expressing different chemosensory receptors demonstrated that both proliferation zones at the ILC and S/NS contribute to the generation of different OSN subpopulations albeit with a quantitative biases. A model is proposed in which adult born OSNs turn on chemoreceptor expression close to their site of birth, migrate radially across the sensory OE and over time undergo cell death, creating the impression of defined ring-like expression domains. A computational model based on quantitative parameters extracted from the analysis of the temporal behaviour of new born OSNs was developed to test whether physical and ontogenetic parameters such as speed of OSN migration, birth rate of the progenitors in the proliferation zones, maturating timing and the lifespan of the OSNs are sufficient to mimic the expression profiles of OR genes.
