A Pak1/Erk signaling module acts through Gata6 to regulate cardiovascular development in zebrafish.
Proper neural crest development and migration is critical during embryonic development, but the molecular mechanisms regulating this process remain incompletely understood. Here, we show that the protein kinase Erk, which plays a central role in a number of key developmental processes in vertebrates, is regulated in the developing neural crest by p21-activated protein kinase 1 (Pak1). Furthermore, we show that activated Erk signals by phosphorylating the transcription factor Gata6 on a conserved serine residue to promote neural crest migration and proper formation of craniofacial structures, pigment cells, and the outflow tract of the heart. Our data suggest an essential role for Pak1 as an Erk activator, and Gata6 as an Erk target, during neural crest development.
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Department of Biochemistry and Molecular Biology, Drexel University, Philadelphia, PA 19102, USA.
Mollie L
ML
Kelly
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Artyom
A
Astsaturov
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Jennifer
J
Rhodes
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Electronic address: jonathan.chernoff@fccc.edu.
Jonathan
J
Chernoff
D000818:Animals; D018376:Cardiovascular Abnormalities / Q000235:genetics; D002319:Cardiovascular System / Q000196:embryology*; D002465:Cell Movement; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006321:Heart / Q000196:embryology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D060172:Morpholinos / Q000235:genetics; D009432:Neural Crest / Q000196:embryology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
D050980:GATA Transcription Factors; C525956:Gata6 protein, zebrafish; D060172:Morpholinos; D029961:Zebrafish Proteins; D054462:p21-Activated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; C554141:MAP2K1 protein, zebrafish