The Drosophila Ste20-related kinase misshapen is required for embryonic dorsal closure and acts through a JNK MAPK module on an evolutionarily conserved signaling pathway

Abstract

Dorsal closure in the Drosophila embryo occurs during the later stages of embryogenesis and involves changes in cell shape leading to the juxtaposition and subsequent adherence of the lateral epidermal primordia over the amnioserosa. Dorsal closure requires the activation of a conserved c-jun amino-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) module, as it is blocked by null mutations in JNK kinase [hemipterous (hep)] and JNK [basket (bsk)]. Drosophila JNK (DJNK) functions by phosphorylating and activating DJun, which in turn induces the transcription of decapentaplegic (dpp). We provide biochemical and genetic evidence that a Ste20-related kinase,misshapen (msn), functions upstream of hep andbsk to stimulate dorsal closure in the Drosophilaembryo. Mammalian (NCK-interactingkinase [NIK]) and Caenorhabditis elegans(mig-15) homologs of msn have been identified;mig-15 is necessary for several developmental processes inC. elegans. These data suggest that msn, mig-15, and NIK are components of a signaling pathway that is conserved among flies, worms, and mammals to control developmentally regulated pathways.

Keywords

• Drosophila
• Ste20 kinase
• NIK
• misshapen
• dorsal closure
• JNK