ZFIN ID: ZDB-PUB-071210-38
Disruption of Esrom and Ryk identifies the roof plate boundary as an intermediate target for commissure formation
Hendricks, M., Mathuru, A.S., Wang, H., Silander, O., Kee, M.Z., and Jesuthasan, S.
Date: 2008
Source: Molecular and cellular neurosciences   37(2): 271-283 (Journal)
Registered Authors: Hendricks, Michael, Jesuthasan, Suresh, Wang, Hui
Keywords: Midline crossing, Habenula, Guidepost, Receptor localization, Commissure, Phr1, PAM, Mycbp2, Eph, Tsc2, Scaffold, Wnt, 4E-BP1
MeSH Terms:
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Cells, Cultured
  • Down-Regulation/genetics
  • Functional Laterality/physiology
  • Gene Expression Regulation, Developmental/genetics
  • Growth Cones/metabolism*
  • Growth Cones/ultrastructure
  • Habenula/cytology
  • Habenula/embryology*
  • Habenula/metabolism
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Microscopy, Video
  • Mixed Function Oxygenases/genetics
  • Mixed Function Oxygenases/metabolism*
  • Neural Pathways/cytology
  • Neural Pathways/embryology
  • Neural Pathways/metabolism
  • Rabbits
  • Receptor Protein-Tyrosine Kinases/genetics
  • Receptor Protein-Tyrosine Kinases/metabolism*
  • Receptors, Eph Family/genetics
  • Receptors, Eph Family/metabolism
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Wnt4 Protein
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 18060805 Full text @ Mol. Cell Neurosci.
Growth cones are guided to their final destination by intermediate targets. Here, we identify intermediate targets and signaling components acting on zebrafish habenula commissural axons. Live imaging establishes that axons pause at the medial habenula before and after crossing the roof plate. esrom mutants axons fail to advance beyond the ipsilateral medial habenula. Tsc2 function is reduced in mutant axons, indicating cell autonomous defects in signaling. Consistent with signaling properties changing outside the roof plate, EphB is surface localized on axon segments within a zone demarcated by the medial habenula. wnt4a is expressed in the medial habenula and morpholino knockdown causes loss of the commissure. Electroporation of truncated Ryk causes axons to reenter the midline after reaching the contralateral habenula. These data identify Esrom as a mediator of growth cone navigation at an intermediate target and underscore the importance of midline boundaries as signaling centers for commissure formation.