Convergent extension (CE) is a morphogenetic process during which cells within a layer intercalate (converge), making the layer longer and thinner(extended) as a result. CE is important for diverse morphogenetic events, from gastrulation to organogenesis. In this issue, two articles identify new regulators of CE with potential implications for human hereditary disorders.
On p. 2121, Zhang,Shi and colleagues report that Down syndrome critical region protein 5 (Dscr5)regulates CE through non-canonical Wnt/planar cell polarity (PCP) signalling during zebrafish gastrulation. Dscr5 is encoded on a chromosomal region crucial to Down syndrome pathogenesis in humans and functions in glycosylphosphatidylinositol (GPI) biosynthesis. The authors show that both dscr5 overexpression and morpholino knockdown impair CE, but not embryonic patterning. Dscr5 is also required for the cell surface localization of Knypek/Glypican 4. Glypicans, heparan sulfate proteoglycans that promote PCP signalling by facilitating Wnt interactions with signalling receptors,contain GPI membrane anchors, and these findings indicate for the first time that glypican function is linked to GPI biosynthesis. Dscr5 knockdown also promotes endocytosis of the Wnt receptor Frizzled 7 and the degradation of the PCP pathway component Dishevelled. Thus, Dscr5 appears to regulate CE by allowing glypican and Wnt receptor interaction at the cell surface, thereby also preventing Dishevelled degradation.
On p. 1977, Norio Yamamoto and colleagues identify CE as being important for mouse inner ear patterning. Mammals detect sounds through the organ of Corti (OC), an inner ear structure that contains highly ordered rows of auditory sensory cells, but the mechanisms that control OC cellular patterning are unclear. By measuring tissue and cell size and shape, the authors establish that during OC development, CE movements occur. They also find that non-muscle myosin II(NMII) is distributed asymmetrically in the developing sensory cells, and that inhibiting NMII genetically and pharmacologically leads to defects in OC CE movements. Based on these data, the authors propose that NMII is a key regulator of OC patterning and suggest that this might explain the hearing defects of humans with myosin mutations. The results of these two studies shed new light on CE regulation and on its importance in development and disease.