title: Integrin-α5 coordinates assembly of posterior cranial placodes in zebrafish and enhances Fgf-dependent regulation of otic/epibranchial cells.
abstract: Vertebrate sensory organs develop in part from cranial placodes, a series of ectodermal thickenings that coalesce from a common domain of preplacodal ectoderm. Mechanisms coordinating morphogenesis and differentiation of discrete placodes are still poorly understood. We have investigated whether placodal assembly in zebrafish requires Integrin- α5 (itga5), an extracellular matrix receptor initially expressed throughout the preplacodal ectoderm. Morpholino knockdown of itga5 had no detectable effect on anterior placodes (pituitary, nasal and lens), but posterior placodes developed abnormally, resulting in disorganization of trigeminal and epibranchial ganglia and reduction of the otic vesicle. Cell motion analysis in GFP-transgenic embryos showed that cell migration in itga5 morphants was highly erratic and unfocused, impairing convergence and blocking successive recruitment of new cells into these placodes. Further studies revealed genetic interactions between itga5 and Fgf signaling. First, itga5 morphants showed changes in gene expression mimicking modest reduction in Fgf signaling. Second, itga5 morphants showed elevated apoptosis in the otic/epibranchial domain, which was rescued by misexpression of Fgf8. Third, knockdown of the Fgf effector erm had no effect by itself but strongly enhanced defects in itga5 morphants. Finally, proper regulation of itga5 requires dlx3b/4b and pax8, which are themselves regulated by Fgf. These findings support a model in which itga5 coordinates cell migration into posterior placodes and augments Fgf signaling required for patterning of these tissues and cell survival in otic/epibranchial placodes.
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Neha
authors.initials: N
authors.lastname: Bhat
authors.forename: Bruce B
authors.initials: BB
authors.lastname: Riley
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002465:Cell Movement; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism; D004475:Ectoderm / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D039482:Integrin alpha5 / Q000502:physiology*; D009024:Morphogenesis / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D039482:Integrin alpha5; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D029961:Zebrafish Proteins; C513244:etv5b protein, zebrafish; D049452:Green Fluorescent Proteins; D005346:Fibroblast Growth Factors