Hecate/Grip2a Acts to Reorganize the Cytoskeleton in the Symmetry-Breaking Event of Embryonic Axis Induction

作者：Xiaoyan Ge, Danielle Ann Grotjahn, Elaine L. Welch, Jamie Lyman‐Gingerich, Christiana Holguin, Eva Dimitrova, Elliott W. Abrams, Tripti Gupta, Florence L. Marlow, Taijiro Yabe, Anna Adler, Mary C. Mullins, Francisco J. Pelegri · 发表于：PLoS Genetics · 年份：2014 · DOI：10.1371/journal.pgen.1004422 · 被引用次数：56 · 研究领域：Reproductive Biology and Fertility、Developmental Biology and Gene Regulation、Microtubule and mitosis dynamics

Maternal homozygosity for three independent mutant hecate alleles results in embryos with reduced expression of dorsal organizer genes and defects in the formation of dorsoanterior structures. A positional cloning approach identified all hecate mutations as stop codons affecting the same gene, revealing that hecate encodes the Glutamate receptor interacting protein 2a (Grip2a), a protein containing multiple PDZ domains known to interact with membrane-associated factors including components of the Wnt signaling pathway. We find that grip2a mRNA is localized to the vegetal pole of the oocyte and early embryo, and that during egg activation this mRNA shifts to an off-center vegetal position corresponding to the previously proposed teleost cortical rotation. hecate mutants show defects in the alignment and bundling of microtubules at the vegetal cortex, which result in defects in the asymmetric movement of wnt8a mRNA as well as anchoring of the kinesin-associated cargo adaptor Syntabulin. We also find that, although short-range shifts in vegetal signals are affected in hecate mutant embryos, these mutants exhibit normal long-range, animally directed translocation of cortically injected dorsal beads that occurs in lateral regions of the yolk cortex. Furthermore, we show that such animally-directed movement along the lateral cortex is not restricted to a single arc corresponding to the prospective dorsal region, but occur in multiple meridional arcs even in opposite regions of the ...