PMID:25514037

Citation	Abu-Issa, R (2015) Rac1 modulates cardiomyocyte adhesion during mouse embryonic development. Biochem. Biophys. Res. Commun. 456:847-52
Abstract	Rac1, a member of the Rho subfamily of small GTPases, is involved in morphogenesis and differentiation of many cell types. Here we define a role of Rac1 in cardiac development by specifically deleting Rac1 in the pre-cardiac mesoderm using the Nkx2.5-Cre transgenic driver line. Rac1-conditional knockout embryos initiate heart development normally until embryonic day 11.5 (E11.5); their cardiac mesoderm is specified, and the heart tube is formed and looped. However, by E12.5-E13.5 the mutant hearts start failing and embryos develop edema and hemorrhage which is probably the cause for the lethality observed soon after. The hearts of Rac1-cKO embryos exhibit disorganized and thin myocardial walls and defects in outflow tract alignment. No significant differences of cardiomyocyte death or proliferation were found between developing control and mutant embryos. To uncover the role of Rac1 in the heart, E11.5 primary heart cells were cultured and analyzed in vitro. Rac1-deficient cardiomyocytes were less spread, round and loosely attached to the substrate and to each other implying that Rac1-mediated signaling is required for appropriate cell-cell and/or cellmatrix adhesion during cardiac development.
Links	PubMed Online version:10.1016/j.bbrc.2014.12.042
Keywords	Animals; Apoptosis; Cell Adhesion; Cell Proliferation; Cell Survival; Embryonic Development; Female; Genotype; Heart Defects, Congenital/embryology; Heart Defects, Congenital/pathology; Integrases/metabolism; Male; Mice, Knockout; Mutation/genetics; Myocytes, Cardiac/metabolism; Myocytes, Cardiac/pathology; rac1 GTP-Binding Protein/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:RAC1		GO:0061344: regulation of cell adhesion involved in heart morphogenesis	ECO:0000315:		P		Figure 3 shows cell adhesion defects in Rac1-cKO mice. "The observed adhesion defects are manifested only after E12.5 even though cardiomyocytes differentiate and start contracting few days earlier at E8.5... The ‘in vitro’ results demonstrate that cardiomyocytes present adhesion defects at E11.5, however, cardiomyocyte adhesion is not completely abolished as these cells still do weakly adhere to the substrate and one another. This suggests that Rac1 is not required for initial adhesion, but is needed for enhancement and maturation of adhesive properties of cardiomyocytes when the heart beating begins to carry higher loads at E12.5 and beyond."	complete CACAO 11086

References

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