Multicellular organisms arise through the generation of different cell types and the organization of cells into tissues and organs. transitions between these two states in the early mouse embryo are discussed in this review. genes leading to basement membrane degradation.18 Recently another pathway has been described in chick embryos involving Net1 an activator of RhoA. Loss of Net1 prior to EMT reduces basal RhoA levels causing basal microtubule destabilization and collapse of the epithelial cell-basal membrane junctions thereby Ginsenoside Rb2 leading to the breakdown of the membrane.19 When cells at the primitive streak start ingressing they elongate and acquire a bottle shape by narrowing their apical surface while maintaining their contacts to neighboring cells. Nuclei and mitochondria are mostly displaced apically while the cytoplasm bulges basally. Cells protrude filopodia basally towards the underlying endoderm. 16 To maintain epithelial integrity epiblast cells may vault over ingressing mesoderm cells as has been described in rabbits.17 Bottle shaped cells progressively lose their contact with the apical surface as finger-like projections of surrounding epiblast cells bridge over the ingressing cell and meet apically enclosing the ingressing cell. Therefore when an ingressing cell breaks down its adherens junctions to neighboring epiblast cells epithelial continuity is maintained as cells remaining in the epithelium seal the gap by establishing new adherens junctions. Once cells detach from the epiblast layer they round up as they traverse the primitive streak. These carefully orchestrated changes in cell shape are likely to be driven by cytoskeletal rearrangements. To this end the gastrulation defects observed in the mouse mutant and demarcates the region of primitive streak formation. mutants fail to form a primitive streak23 as do β-catenin-deficient embryos as well as Wnt receptor compound mutants.24 25 Conversely stabilized β-catenin leads to premature EMT in the epiblast 26 while mutants lacking form ectopic primitive streaks.30 Moreover compound mutants two TGFβ family ligands show affected mesoderm induction with variable expressivity.31 In the chick the decision for a cell to ingress relies on FGF signaling. Tightly regulated expression of Churchill Esam an FGF-induced zinc-finger transcription activator is Ginsenoside Rb2 involved in determining which epiblast cells will ingress and form mesoderm and which will remain in the epiblast thereby adopting a neural fate.32 In a subsequent step once cells have started ingressing FGF signaling is required to maintain mesoderm formation and EMT. In mutant embryos epiblast cells undergo an EMT but cells are unable to migrate away from the primitive streak.33 Loss of (at the primitive streak. Snail1 has been shown to repress expression by binding to E-box sequences within the promoter.2 35 mutants form an aberrant mesodermal layer where cells emerge from the primitive streak but continue to express and retain apical-basal polarity and an epithelial Ginsenoside Rb2 morphology.36 Loss of function studies in other model systems further support the key role of Snail in EMT during gastrulation.37 38 Whereas and expression and therefore control EMT. Conditional inactivation of the T-box factor in the epiblast results in EMT arrest. Ginsenoside Rb2 In these mutants even though and are normally expressed E-cadherin is only partially downregulated suggesting a role for Eomesodermin in enhancing Snail-dependent downregulation perhaps by activating Snail transcriptional partners or in epigenetic reprogramming.39 Downregulation of E-cadherin at the site of ingression is not only controlled at the transcriptional level but also at the post-translational level. Disruption of p38 MAP kinase activation due to loss of p38-interacting protein leads to severe gastrulation defects.40 These proteins act downstream of the NCK-interacting kinase/Map4ke (NIK) loss of Ginsenoside Rb2 which also results in mesoderm cells accumulating at the primitive streak.41 This pathway controls E-cadherin expression by downregulating or destabilizing protein levels in an FGF-signaling independent way ensuring precise control of E-cadherin during the EMT process. As soon as cells have undergone EMT and reach the mesodermal layer they migrate away from the primitive streak as two bilateral wings of mesoderm. In amniotes the different mesodermal cell lineages become specified and allocated according to the time and site of ingression at the primitive streak.42 43 Identity of the different mesodermal fates has been.