Dbx1b defines the dorsal habenular progenitor domain in the zebrafish epithalamus

Abstract

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.

Asymmetry of the Brain: Development and Implications

“…Indeed, Fgf8 is required for habenular neurogenesis, as mutations in the gene result in reduced habenulae in both zebrafish and mouse (106,134). This role of Fgf8 might involve its ability to control the expression of the Dbx1b transcription factor, specifically in progenitors of the dorsal habenular (40). Another putative target of the Nodal pathway could be the Hedgehog pathway, which has also been implicated in development of the epithalamus in mouse and zebrafish (27, 72a).…”

FGF activity asymmetrically regulates the timing of habenular neurogenesis in a Nodal-dependent manner

“…FGF activity was higher in the right habenula and lower in the left habenula ( Figure 1B). To confirm that asymmetric FGF activity was in the habenulae, we analyzed the co-expression of this transgene with the recently reported dHb progenitor marker, dbx1b (Dean et al, 2014). Single optical sections reveal that asymmetric FGF signaling is present in the early habenula ( Figure 1C&D).…”

Genome Wide Analysis for Growth at Two Growth Stages in A New Fast-Growing Common Carp Strain (Cyprinus carpio L.)

“…Rotein kinase C-binding protein (NELL2) promotes survival of neurons 37 . Homeobox protein (DBX1-B) is crucial for production of dorsal habenular neurons 38 . Synapse differentiation-inducing gene protein 1 (SYNDIG1) regulates the excitatory synapse maturation in rats 39 .…”