PUBLICATION

Hedgehog signalling maintains the optic stalk-retinal interface through the regulation of Vax gene activity

Authors
Take-uchi, M., Clarke, J.D.W., and Wilson, S.W.
ID
ZDB-PUB-030210-6
Date
2003
Source
Development (Cambridge, England)   130(5): 955-968 (Journal)
Registered Authors
Clarke, Jon, Take-uchi, Masaya, Wilson, Steve
Keywords
none
MeSH Terms
  • Animals
  • Body Patterning
  • Coloboma/pathology
  • Eye Proteins*
  • Gene Expression Regulation
  • Gene Expression Regulation, Developmental*
  • Genes, Homeobox
  • Hedgehog Proteins
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Humans
  • In Situ Hybridization
  • Neuropeptides/genetics
  • Neuropeptides/metabolism*
  • Nodal Protein
  • Optic Nerve/anatomy & histology
  • Optic Nerve/embryology*
  • Optic Nerve/physiology
  • Phylogeny
  • Receptors, Cell Surface/metabolism
  • Receptors, Fibroblast Growth Factor/metabolism
  • Receptors, G-Protein-Coupled*
  • Recombinant Fusion Proteins/metabolism
  • Retina/anatomy & histology
  • Retina/embryology*
  • Retina/physiology
  • Signal Transduction/physiology*
  • Trans-Activators/genetics
  • Trans-Activators/metabolism*
  • Transforming Growth Factor beta/metabolism
  • Xenopus Proteins*
  • Zebrafish/anatomy & histology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins*
PubMed
12538521 Full text @ Development
Abstract
During early formation of the eye, the optic vesicle becomes partitioned into a proximal domain that forms the optic nerve and a distal domain that forms the retina. In this study, we investigate the activity of Nodal, Hedgehog (Hh) and Fgf signals and Vax family homeodomain proteins in this patterning event. We show that zebrafish vax1 and vax2 are expressed in overlapping domains encompassing the ventral retina, optic stalks and preoptic area. Abrogation of Vax1 and Vax2 activity leads to a failure to close the choroid fissure and progressive expansion of retinal tissue into the optic nerve, finally resulting in a fusion of retinal neurons and pigment epithelium with forebrain tissue. We show that Hh signals acting through Smoothened act downstream of the Nodal pathway to promote Vax gene expression. However, in the absence of both Nodal and Hh signals, Vax genes are expressed revealing that other signals, which we show include Fgfs, contribute to Vax gene regulation. Finally, we show that Pax2.1 and Vax1/Vax2 are likely to act in parallel downstream of Hh activity and that the bel locus (yet to be cloned) mediates the ability of Hh-, and perhaps Fgf-, signals to induce Vax expression in the preoptic area. Taking all these results together, we present a model of the partitioning of the optic vesicle along its proximo-distal axis.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping