Lifelong neurogenesis in vertebrates relies on stem cells producing proliferation zones that contain neuronal precursors with distinct fates. Proliferation zones in the adult zebrafish brain are located in distinct regions along its entire anterior-posterior axis. We show a previously unappreciated degree of conservation of brain proliferation patterns among teleosts, suggestive of a teleost ground plan. Pulse chase labeling of proliferating populations reveals a centrifugal movement of cells away from their places of birth into the surrounding mantle zone. We observe tangential migration of cells born in the ventral telencephalon, but only a minor rostral migratory stream to the olfactory bulb. In contrast, the lateral telencephalic area, a domain considered homologous to the mammalian dentate gyrus, shows production of interneurons and migration as in mammals. After a 46-day chase, newborn highly mobile cells have moved into nuclear areas surrounding the proliferation zones. They often show HuC/D immunoreactivity but importantly also more specific neuronal identities as indicated by immunoreactivity for tyrosine hydroxylase, serotonin and parvalbumin. Application of a second proliferation marker allows us to recognize label-retaining, actively cycling cells that remain in the proliferation zones. The latter population meets two key criteria of neural stem cells: label retention and self renewal.

In the present study, we describe the structure and normal development of the zebrafish (Danio rerio) paired fins. Particularly, we focus on the structure of the apical epidermis and on endoskeletal morphogenesis. Endoskeletal development proceeds differently in the pectoral and pelvic fins. Whereas in both fins major parts of the endoskeletal girdle develop within the fin bud mesenchyme, the pattern of chondrogenic condensations observed in the pelvic fins directly reflects the adult endoskeletal pattern. In the pectoral fin, a morphogenetic detour is taken via a functional larval endoskeleton, the endoskeletal disc. It arises in the fin bud mesenchyme from a chondrogenic anlage common with the girdle. The disc chondrifies and represents the functional endoskeleton of the larval pectoral fin. The pectoral fin endoskeleton is expanded as well as restructured during larval stages in a process which involves decomposition of cartilage matrix in the endoskeletal disc. Our comparisons of apical fold morphology with reports on other teleosts and tetrapod apical ridges show them to be homologous on the structural level. Comparisons of endoskeletal development of the zebrafish with reports on teleosts, actinopterygians and chondrichthyans show that endoskeletal morphogenesis in the zebrafish pectoral fin follows a morphogenetic process which is wide-spread among actinopterygians.

In the adult CNS, neurogenesis takes place in special niches. It is not understood how these niches are formed during development and how they are maintained. In contrast to mammals, stem cell niches are abundant in zebrafish and also found in other parts of the brain than telencephalon. To understand common characteristics of neural stem cell niches in vertebrates, we studied the origin and architecture of a previously unknown stem cell niche using transgenic lines, in vivo imaging, and marker analysis. We show that bipotent stem cells are maintained in a distinct niche in the adult zebrafish cerebellum. Remarkably, the stem cells are not typical glia but instead retain neuroepithelial characteristics. The cerebellar stem cell niche is generated by the coordinated displacement of ventricle and rhombic lip progenitors in a two-step process involving morphogenetic movements and tissue growth. Importantly, the niche and its stem cells still remain in ventricular contact through a previously unknown derivative of the ventricle. Factors propagated in the ventricle are thought to be important regulators of stem cell activity. To test the requirements of one family of important factors, Fibroblast growth factors, we used zebrafish with an inducible dominant-negative Fgf receptor. Inhibition of Fgf signaling leads to significant reduction of stem cell activity. In contrast to the predominant view, adult neural stem cells in nonmammalian vertebrates show more neuroepithelial than glial characteristics. Nevertheless, retained epithelial properties such as distinct polarization and ventricular contact are critical common determinants to maintain neural stem cell activity in vertebrates.

At birth or after hatching from the egg, vertebrate brains still contain neural stem cells which reside in specialized niches. In some cases, these stem cells are deployed for further postnatal development of parts of the brain until the final structure is reached. In other cases, postnatal neurogenesis continues as constitutive neurogenesis into adulthood leading to a net increase of the number of neurons with age. Yet, in other cases, stem cells fuel neuronal turnover. An example is protracted development of the cerebellar granular layer in mammals and birds, where neurogenesis continues for a few weeks postnatally until the granular layer has reached its definitive size and stem cells are used up. Cerebellar growth also provides an example of continued neurogenesis during adulthood in teleosts. Again, it is the granular layer that grows as neurogenesis continues and no definite adult cerebellar size is reached. Neuronal turnover is most clearly seen in the telencephalon of male canaries, where projection neurons are replaced in nucleus high vocal centre each year before the start of a new mating season--circuitry reconstruction to achieve changes of the song repertoire in these birds? In this review, we describe these and other examples of adult neurogenesis in different vertebrate taxa. We also compare the structure of the stem cell niches to find common themes in their organization despite different functions adult neurogenesis serves in different species. Finally, we report on regeneration of the zebrafish telencephalon after injury to highlight similarities and differences of constitutive neurogenesis and neuronal regeneration.

No abstract