Alk8 is required for neural crest cell formation and development of pharyngeal arch cartilages.
The type I TGFbeta family member receptor alk8 acts in bone morphogenetic protein (BMP) signaling pathways to establish dorsoventral patterning in the early zebrafish embryo. Here, we present evidence that alk8 is required for neural crest cell (NCC) formation and that alk8 signaling gradients direct the proper patterning of premigratory NCCs. We extend our previous functional studies of alk8 to demonstrate that ectopic expression of constitutively active and dominant negative Alk8, consistently results in more medially or laterally positioned premigratory NCCs, respectively. We also demonstrate that patterning defects in premigratory NCCs, induced by alk8 misexpression, correlate with subsequent defects in NCC-derived pharyngeal arch cartilages. Furthermore, an anteroposterior effect is revealed, where overexpression of Alk8 more severely affects anterior arch cartilages and decreased Alk8 activity more severely affects posterior arch cartilage formation. Ectopic expression studies of alk8 are supported by analyses of zygotic and maternal-zygotic laf/alk8 mutants and of several BMP pathway mutants. Pharyngeal mesodermal and endodermal defects in laf/alk8 mutants suggest additional roles for alk8 in patterning of these tissues. Our results provide insight into alk8-mediated BMP signaling gradients and the establishment of premigratory NCC mediolateral positioning, and extend the model for BMP patterning of the neural crest to include that of NCC-derived pharyngeal arch cartilages.
Payne-Ferreira
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TL
Department of Cytokine Biology, The Forsyth Institute, Boston, Massachusetts 02115, USA.
Yelick
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PC
D030201:Activin Receptors, Type I / Q000502:physiology*; D000423:Alcian Blue / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D001934:Branchial Region / Q000196:embryology*; D002356:Cartilage / Q000196:embryology* / Q000378:metabolism; D002465:Cell Movement; D004396:Coloring Agents / Q000494:pharmacology; D004475:Ectoderm / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005799:Genes, Dominant; D005838:Genotype; D020287:In Situ Nick-End Labeling; D009154:Mutation; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D012333:RNA, Messenger / Q000378:metabolism; D012249:Rhombencephalon / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
D004396:Coloring Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D030201:Activin Receptors, Type I; C424203:acvr1l protein, zebrafish; D000423:Alcian Blue