PUBLICATION
Convergence of signaling pathways underlying habenular formation and axonal outgrowth
- Authors
- Roberson, S., Halpern, M.E.
- ID
- ZDB-PUB-170618-19
- Date
- 2017
- Source
- Development (Cambridge, England) 144(14): 2652-2662 (Journal)
- Registered Authors
- Halpern, Marnie E., Roberson, Sara
- Keywords
- Chemokine, Fgf, Habenula, Interpeduncular nucleus, Shh, Wnt
- MeSH Terms
-
- Animals, Genetically Modified
- Wnt Signaling Pathway
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Habenula/embryology*
- Habenula/metabolism*
- Neural Stem Cells/cytology
- Neural Stem Cells/metabolism
- Neurogenesis/genetics
- Neurogenesis/physiology
- Axons/metabolism
- Animals
- Chemokines/genetics
- Chemokines/metabolism
- Hedgehog Proteins/genetics
- Hedgehog Proteins/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Fibroblast Growth Factors/genetics
- Fibroblast Growth Factors/metabolism
- Mutation
- Signal Transduction
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Receptors, CXCR4/genetics
- Receptors, CXCR4/metabolism
- PubMed
- 28619821 Full text @ Development
Citation
Roberson, S., Halpern, M.E. (2017) Convergence of signaling pathways underlying habenular formation and axonal outgrowth. Development (Cambridge, England). 144(14):2652-2662.
Abstract
The habenular nuclei are a conserved integrating center in the vertebrate epithalamus, where they modulate diverse behaviors. Despite their importance, our understanding of habenular development is incomplete. Time-lapse imaging and fate mapping demonstrate that the dorsal habenulae (dHb) of zebrafish are derived from dbx1b-expressing (dbx1b+ ) progenitors, which transition into cxcr4b-expressing neuronal precursors. The precursors give rise to differentiated neurons, the axons of which innervate the midbrain interpeduncular nucleus (IPN). Formation of the dbx1b+ progenitor population relies on the activity of the Shh, Wnt and Fgf signaling pathways. Wnt and Fgf function additively to generate dHb progenitors. Surprisingly, Wnt signaling also negatively regulates fgf8a, confining expression to a discrete dorsal diencephalic domain. Moreover, the Wnt and Fgf pathways have opposing roles in transcriptional regulation of components of the Cxcr4-chemokine signaling pathway. The chemokine pathway, in turn, directs the posterior outgrowth of dHb efferents toward the IPN and, when disrupted, results in ectopic, anteriorly directed axonal projections. The results define a signaling network underlying the generation of dHb neurons and connectivity with their midbrain target.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping