title: Hedgehog signalling maintains the optic stalk-retinal interface through the regulation of Vax gene activity.
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.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK. m.take-uchi@ucl.ac.uk, s.wilson@ucl.ac.uk
authors.forename: Masaya
authors.initials: M
authors.lastname: Take-uchi
authors.forename: Jonathan D W
authors.initials: JD
authors.lastname: Clarke
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wilson
mesh_terms: D000818:Animals; D019521:Body Patterning; D003103:Coloboma / Q000473:pathology; D005136:Eye Proteins; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D055457:Nodal Protein; D009900:Optic Nerve / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology; D010802:Phylogeny; D011956:Receptors, Cell Surface / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012160:Retina / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000072086:Smoothened Receptor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D029867:Xenopus Proteins; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins
chemical_list: D005136:Eye Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C526007:NODAL protein, human; D009479:Neuropeptides; D055457:Nodal Protein; C526008:Nodal protein, mouse; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; C491023:SMO protein, human; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C492362:VAX2 protein, human; C485177:Vax1 protein, mouse; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C491021:smo protein, zebrafish; C485179:vax1 protein, zebrafish; C492361:vax2 protein, Xenopus