Repression of Wasp by JAK/STAT signalling inhibits medial actomyosin network assembly and apical cell constriction in intercalating epithelial cells

Development. 2009 Dec;136(24):4199-212. doi: 10.1242/dev.040402.

Abstract

Tissue morphogenesis requires stereotyped cell shape changes, such as apical cell constriction in the mesoderm and cell intercalation in the ventrolateral ectoderm of Drosophila. Both processes require force generation by an actomyosin network. The subcellular localization of Myosin-II (Myo-II) dictates these different morphogenetic processes. In the intercalating ectoderm Myo-II is mostly cortical, but in the mesoderm Myo-II is concentrated in a medial meshwork. We report that apical constriction is repressed by JAK/STAT signalling in the lateral ectoderm independently of Twist. Inactivation of the JAK/STAT pathway causes germband extension defects because of apical constriction ventrolaterally. This is associated with ectopic recruitment of Myo-II in a medial web, which causes apical cell constriction as shown by laser nanosurgery. Reducing Myo-II levels rescues the JAK/STAT mutant phenotype, whereas overexpression of the Myo-II heavy chain (also known as Zipper), or constitutive activation of its regulatory light chain, does not cause medial accumulation of Myo-II nor apical constriction. Thus, JAK/STAT controls Myo-II localization by additional mechanisms. We show that regulation of actin polymerization by Wasp, but not by Dia, is important in this process. Constitutive activation of Wasp, a branched actin regulator, causes apical cell constriction and promotes medial 'web' formation. Wasp is inactivated at the cell cortex in the germband by JAK/STAT signalling. Lastly, wasp mutants rescue the normal cortical enrichment of Myo-II and inhibit apical constriction in JAK/STAT mutants, indicating that Wasp is an effector of JAK/STAT signalling in the germband. We discuss possible models for the role of Wasp activity in the regulation of Myo-II distribution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism
  • Animals
  • Cell Polarity / physiology
  • Cytoskeleton / metabolism
  • Drosophila / embryology
  • Drosophila / physiology*
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / physiology*
  • Ectoderm / embryology
  • Ectoderm / physiology
  • Epithelial Cells* / cytology
  • Epithelial Cells* / physiology
  • Janus Kinases / physiology
  • Mesoderm / embryology
  • Mesoderm / physiology
  • Morphogenesis / physiology
  • Myosin Type II / physiology
  • STAT Transcription Factors / physiology
  • Signal Transduction*
  • Wiskott-Aldrich Syndrome Protein / antagonists & inhibitors
  • Wiskott-Aldrich Syndrome Protein / physiology*

Substances

  • Drosophila Proteins
  • STAT Transcription Factors
  • WASp protein, Drosophila
  • Wiskott-Aldrich Syndrome Protein
  • Actomyosin
  • Janus Kinases
  • Myosin Type II