Dachsous1b cadherin regulates actin and microtubule cytoskeleton during early zebrafish embryogenesis

Abstract

Dachsous (Dchs), an atypical cadherin, is an evolutionarily conserved regulator of planar cell polarity, tissue size, and cell adhesion. In humans, DCHS1 mutations cause pleiotropic Van Maldergem syndrome. Here, we report that mutations in zebrafish dchs1b and dchs2 disrupt several aspects of embryogenesis, including gastrulation. Unexpectedly, maternal zygotic (MZ) dchs1b mutants show defects in the earliest developmental stage, egg activation, including abnormal cortical granule exocytosis (CGE), cytoplasmic segregation, cleavages, and maternal mRNA translocation, in transcriptionally quiescent embryos. Later, MZdchs1b mutants exhibit altered dorsal organizer and mesendodermal gene expression, due to impaired dorsal determinant transport and Nodal signaling. Mechanistically, MZdchs1b phenotypes can be explained in part by defective actin or microtubule networks, which appear bundled in mutants. Accordingly, disruption of actin cytoskeleton in wild-type embryos phenocopied MZdchs1b mutant defects in cytoplasmic segregation and CGE. Whereas, interfering with microtubules in wild-type embryos impaired dorsal organizer and mesodermal gene expression without perceptible earlier phenotypes. Moreover, the bundled microtubule phenotype was partially rescued by expressing either full-length Dchs1b or its intracellular domain, suggesting Dchs1b affects microtubules and some developmental processes independent of its known ligand Fat. Our results indicate novel roles for vertebrate Dchs in actin and microtubule cytoskeleton regulation in the unanticipated context of the single-celled embryo.

Modulation of F-actin dynamics by maternal Mid1ip1L controls germ plasm aggregation and furrow recruitment in the zebrafish embryo

“…However, the bulk of ooplasmic streaming into the blastodisc occurs through internal yolk cell channels, likely generating a central-to-peripheral flow in the blastodisc (e.g. Li-Villarreal et al, 2015). Such a flow would be unlikely to contribute to RNP retention, which we infer occurs in the opposite direction.…”

“…During the early cell cycles in the zebrafish embryo, intracellular components undergo active redistribution through ooplasmic streaming, a process that depends on F-actin function (Roosen-Runge, 1938;Kane and Kimmel, 1993;Leung et al, 2000;Fernández et al, 2006;Fuentes and Fernández, 2010;Li-Villarreal et al, 2015). We cannot rule out scenarios in which Mid1ip1L-and F-actin-mediated RNP retention occurs indirectly through the modulation of cytoplasmic flow.…”

Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

“…6A,B; Fontenille et al, 2014;Jesuthasan and Strähle, 1997;Solnica-Krezel and Driever, 1994). Interestingly, MZ zebrafish mutants of the atypical cadherin Dachsous 1b (Dchs1b) display similar voids in the YCL actin and microtubule cytoskeleton and slow epiboly progression (Li-Villarreal et al, 2015). A similar defect is observed in MZ pou5f3 zebrafish mutant embryos, where a loss of the YCL itself is associated with the microtubule gaps (Lachnit et al, 2008).…”

Maternal Ybx1 safeguards zebrafish oocyte maturation and maternal-to-zygotic transition by repressing global translation

“…2A,B). To further analyze the activation phenotype of mutant eggs, we studied two events that are tightly associated with egg activation: cortical granule (CG) exocytosis and cytoplasmic streaming (Fuentes and Fernández, 2010;Hart, 1990;Li-Villarreal et al, 2015). We labelled CGs using fluoresceinconjugated Maclura pomifera lectin to assess CG exocytosis in activated eggs (Becker and Hart, 1999;Dosch et al, 2004).…”