Differential expression and homotypic enrichment of a classic Cadherin directs tissue-level contractile asymmetry during neural tube closure

Abstract

Embryos pattern force generation at tissue boundaries during morphogenesis, but how they do so remains poorly understood. Here we show how tissue-specific expression of the type II cadherin, Cadherin2 (hereafter Cad2), patterns actomyosin contractility along the neural/epidermal (Ne/Epi) boundary to drive zippering and neural tube closure in the basal chordate, Ciona robusta. Cad2 is differentially expressed and homotypically enriched in neural cells along the Ne/Epi boundary, where RhoA and Myosin are activated during zipper progression. Equalizing Cad2 expression across the Ne/Epi boundary inhibits RhoA/Myosin activation and zipper progression, while creating ectopic Cad2 expression boundaries is sufficient to direct RhoA/Myosin activity to those boundaries. We show that Cad2 polarizes RhoA activity by sequestering the Rho GTPase activating protein, Gap21/23, to homotypic junctions, which in turn redirects RhoA/Myosin activity to heterotypic Ne/Epi junctions. By activating Myosin II along Ne/Epi junctions ahead of zipper and inhibiting Myosin II at new Ne/Ne junctions behind zipper, Cad2 promotes tissue level contractile asymmetry to drive zipper progression.