DEVELOPMENT AND CELLULAR DYNAMICS OF THE ROSTRAL MIGRATORY STREAM

Cellular migration is a fundamental mechanism for brain development, function and potential recovery after injury. The rostral migratory stream (RMS) is characterized by the continuous migration of neuroblasts from neural stem cells (NSCs) of the forebrain to the olfactory bulbs (OB), where they differentiate into neurons. The RMS was first described in adult mammals, though less is known in the highly neurogenic zebrafish model where a similar structure persists. A major knowledge gap concerns the formation and cellular dynamics of the RMS from larval to adult stages, and how it contributes to lifelong OB neurogenesis. Here, we investigated the establishment of the zebrafish RMS over ontogeny.
To characterize the zebrafish RMS over development, we examined NSC activity, migrating progenitors and neurogenic output from the subpallial RMS origin to the OB in larval, juvenile, adult and aging fish. The migration marker PSA-NCAM highlighted the absence of an early RMS, followed by a shift to rostral-specific migration largely supported by blood-vessels. Using reporter lines and electron microscopy we describe an initial expansion of the subpallial NSC pool dominated by neuro-epithelial cells that undergo lifelong cytoarchitectural remodeling. Applying thymidine analogue EdU, we showed a peak in NSC proliferation and migration in juveniles that was attenuated in aged fish. Finally, newborn progenitors exclusively differentiated into GABAergic interneurons in the OB within 2 weeks. Findings from this study offer novel insights towards how NSC populations and their progeny are modified as the RMS develops to its adult form to support OB migration in non-mammalian models.