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Development February 15, 2016; 143 (4): 715-27.

Molecular model for force production and transmission during vertebrate gastrulation.

Pfister K , Shook DR , Chang C , Keller R , Skoglund P .

Vertebrate embryos undergo dramatic shape changes at gastrulation that require locally produced and anisotropically applied forces, yet how these forces are produced and transmitted across tissues remains unclear. We show that depletion of myosin regulatory light chain (RLC) levels in the embryo blocks force generation at gastrulation through two distinct mechanisms: destabilizing the myosin II (MII) hexameric complex and inhibiting MII contractility. Molecular dissection of these two mechanisms demonstrates that normal convergence force generation requires MII contractility and we identify a set of molecular phenotypes correlated with both this failure of convergence force generation in explants and of blastopore closure in whole embryos. These include reduced rates of actin movement, alterations in C-cadherin dynamics and a reduction in the number of polarized lamellipodia on intercalating cells. By examining the spatial relationship between C-cadherin and actomyosin we also find evidence for formation of transcellular linear arrays incorporating these proteins that could transmit mediolaterally oriented tensional forces. These data combine to suggest a multistep model to explain how cell intercalation can occur against a force gradient to generate axial extension forces. First, polarized lamellipodia extend mediolaterally and make new C-cadherin-based contacts with neighboring mesodermal cell bodies. Second, lamellipodial flow of actin coalesces into a tension-bearing, MII-contractility-dependent node-and-cable actin network in the cell body cortex. And third, this actomyosin network contracts to generate mediolateral convergence forces in the context of these transcellular arrays.

PubMed ID: 26884399
PMC ID: PMC4760319
Article link: Development
Grant support: [+]

Species referenced: Xenopus
Genes referenced: actb cdh3 myh10 myl12b myl2 mylip slc25a20
Antibodies: Cdh3 Ab1 Myh10 Ab1 Myl12b/Myl9 Ab1 Phospho- Myl2 Ab1
Morpholinos: myl12b MO1

Article Images: [+] show captions
References [+] :
Aad, Search for Higgs and Z Boson Decays to J/ψγ and ϒ(nS)γ with the ATLAS Detector. 2015, Pubmed