Inca: a novel p21-activated kinase-associated protein required for cranial neural crest development.
Inca (induced in neural crest by AP2) is a novel protein discovered in a microarray screen for genes that are upregulated in Xenopus embryos by the transcriptional activator protein Tfap2a. It has no significant similarity to any known protein, but is conserved among vertebrates. In Xenopus, zebrafish and mouse embryos, Inca is expressed predominantly in the premigratory and migrating neural crest (NC). Knockdown experiments in frog and fish using antisense morpholinos reveal essential functions for Inca in a subset of NC cells that form craniofacial cartilage. Cells lacking Inca migrate successfully but fail to condense into skeletal primordia. Overexpression of Inca disrupts cortical actin and prevents formation of actin "purse strings", which are required for wound healing in Xenopus embryos. We show that Inca physically interacts with p21-activated kinase 5 (PAK5), a known regulator of the actin cytoskeleton that is co-expressed with Inca in embryonic ectoderm, including in the NC. These results suggest that Inca and PAK5 cooperate in restructuring cytoskeletal organization and in the regulation of cell adhesion in the early embryo and in NC cells during craniofacial development.
Luo
Ting
T
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Xu
Yanhua
Y
Hoffman
Trevor L
TL
Zhang
Tailin
T
Schilling
Thomas
T
Sargent
Thomas D
TD
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura / Q000196:embryology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009432:Neural Crest / Q000196:embryology*; D009841:Oligonucleotides; D012886:Skull / Q000196:embryology*; D050656:Transcription Factor AP-2 / Q000378:metabolism; D014981:Xenopus / Q000196:embryology* / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D015003:Yeasts; D015027:Zebrafish / Q000196:embryology; D054462:p21-Activated Kinases / Q000378:metabolism
D000199:Actins; C524507:IncaA protein, Xenopus; D009419:Nerve Tissue Proteins; D009841:Oligonucleotides; D050656:Transcription Factor AP-2; D029867:Xenopus Proteins; C493675:tfap2a protein, Xenopus; C486709:X-PAK5 protein, Xenopus; D054462:p21-Activated Kinases