title: Rac1 mediates morphogenetic responses to intercellular signals in the gastrulating mouse embryo.
abstract: The establishment of the mammalian body plan depends on signal-regulated cell migration and adhesion, processes that are controlled by the Rho family of GTPases. Here we use a conditional allele of Rac1, the only Rac gene expressed early in development, to define its roles in the gastrulating mouse embryo. Embryos that lack Rac1 in the epiblast (Rac1Δepi) initiate development normally: the signaling pathways required for gastrulation are active, definitive endoderm and all classes of mesoderm are specified, and the neural plate is formed. After the initiation of gastrulation, Rac1Δepi embryos have an enlarged primitive streak, make only a small amount of paraxial mesoderm, and the lateral anlage of the heart do not fuse at the midline. Because these phenotypes are also seen in Nap1 mutants, we conclude that Rac1 acts upstream of the Nap1/WAVE complex to promote migration of the nascent mesoderm. In addition to migration phenotypes, Rac1Δepi cells fail to adhere to matrix, which leads to extensive cell death. Cell death is largely rescued in Rac1Δepi mutants that are heterozygous for a null mutation in Pten, providing evidence that Rac1 is required to link signals from the basement membrane to activation of the PI3K-Akt pathway in vivo. Surprisingly, the frequency of apoptosis is greater in the anterior half of the embryo, suggesting that cell survival can be promoted either by matrix adhesion or by signals from the posterior primitive streak. Rac1 also has essential roles in morphogenesis of the posterior notochordal plate (the node) and the midline.
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Migeotte
authors.forename: Joaquim
authors.initials: J
authors.lastname: Grego-Bessa
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Anderson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D005775:Gastrula / Q000502:physiology*; D007211:Indoles; D008648:Mesoderm / Q000196:embryology*; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
chemical_list: D007211:Indoles; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C007293:DAPI; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein