The formation of the embryonic brain requires the production, migration, and differentiation of neurons to be timely and coordinated. Coupling to the photoperiod could synchronize the development of neurons in the embryo. Here, we consider the effect of light and melatonin on the differentiation of embryonic neurons in zebrafish. We examine the formation of neurons in the habenular nuclei, a paired structure found near the dorsal surface of the brain adjacent to the pineal organ. Keeping embryos in constant darkness causes a temporary accumulation of habenular precursor cells, resulting in late differentiation and a long-lasting reduction in neuronal processes (neuropil). Because constant darkness delays the accumulation of the neurendocrine hormone melatonin in embryos, we looked for a link between melatonin signaling and habenular neurogenesis. A pharmacological block of melatonin receptors delays neurogenesis and reduces neuropil similarly to constant darkness, while addition of melatonin to embryos in constant darkness restores timely neurogenesis and neuropil. We conclude that light and melatonin schedule the differentiation of neurons and the formation of neural processes in the habenular nuclei.
BackgroundThe conserved habenular nuclei function as a relay system connecting the forebrain with the brain stem. They play crucial roles in various cognitive behaviors by modulating cholinergic, dopaminergic and serotonergic activities. Despite the renewed interest in this conserved forebrain region because of its importance in regulating aversion and reward behaviors, the formation of the habenular nuclei during embryogenesis is poorly understood due to their small size and deep location in the brain, as well as the lack of known markers for habenular progenitors. In zebrafish, the bilateral habenular nuclei are subdivided into dorsal and ventral compartments, are particularly large and found on the dorsal surface of the brain, which facilitates the study of their development.ResultsHere we examine the expression of a homeodomain transcription factor, dbx1b, and its potential to serve as an early molecular marker of dorsal habenular progenitors. Detailed spatiotemporal expression profiles demonstrate that the expression domain of dbx1b correlates with the presumptive habenular region, and dbx1b-expressing cells are proliferative along the ventricle. A lineage-tracing experiment using the Cre-lox system confirms that all or almost all dorsal habenular neurons are derived from dbx1b-expressing cells. In addition, mutant analysis and pharmacological treatments demonstrate that both initiation and maintenance of dbx1b expression requires precise regulation by fibroblast growth factor (FGF) signaling.ConclusionsWe provide clear evidence in support of dbx1b marking the progenitor populations that give rise to the dorsal habenulae. In addition, the expression of dbx1b in the dorsal diencephalon is tightly controlled by FGF signaling.
The zebrafish pineal complex consists of four cell types (rod and cone photoreceptors, projection neurons and parapineal neurons) that are derived from a single pineal complex anlage. After specification, parapineal neurons migrate unilaterally away from the rest of the pineal complex whereas rods, cones and projection neurons are non-migratory. The transcription factor Tbx2b is important for both the correct number and migration of parapineal neurons. We find that two additional transcription factors, Flh and Nr2e3, negatively regulate parapineal formation. Flh induces non-migratory neuron fates and limits the extent of parapineal specification, in part by activation of Nr2e3 expression. Tbx2b is positively regulated by Flh, but opposes Flh action during specification of parapineal neurons. Loss of parapineal neuron specification in Tbx2b-deficient embryos can be partially rescued by loss of Nr2e3 or Flh function; however, parapineal migration absolutely requires Tbx2b activity. We conclude that cell specification and migration in the pineal complex are regulated by a network of at least three transcription factors.
The highly conserved habenular nuclei in the vertebrate epithalamus function as an integrating center that relaying information between the forebrain and the brain stem.These nuclei play crucial roles in modulating a broad variety of cognitive behaviors.
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