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Essential role for the alpha 1 chain of type VIII collagen in Zebrafish notochord formation
Author(s) -
Gansner John M.,
Gitlin Jonathan D.
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21779
Subject(s) - notochord , biology , zebrafish , mutant , genetics , gene , phenotype , gene knockdown , morphogenesis , microbiology and biotechnology , morpholino , embryogenesis
Several zebrafish mutants identified in large‐scale forward genetic screens exhibit notochord distortion. We now report the cloning and further characterization of one such mutant, gulliver m208 ( gul m208 ). The notochord defect in gul m208 mutants is exacerbated under conditions of copper depletion or lysyl oxidase cuproenzyme inhibition that are without a notochord effect on wild‐type embryos. The gul m208 phenotype results from a missense mutation in the gene encoding Col8a1, a lysyl oxidase substrate, and morpholino knockdown of col8a1 recapitulates the notochord distortion observed in gul m208 mutants. Of interest, the amino acid mutated in gul m208 Col8a1 is highly conserved, and the equivalent substitution in a closely related human protein, COL10A1, causes Schmid metaphyseal chondrodysplasia. Taken together, the data identify a new protein essential for notochord morphogenesis, extend our understanding of gene–nutrient interactions in early development, and suggest that human mutations in COL8A1 may cause structural birth defects. Developmental Dynamics 237:3715–3726, 2008. © 2008 Wiley‐Liss, Inc.