Anterior is up in all images. dominant negative fashion by affecting distribution of other proteins, such as Vangl1 and Pk2 (Track et al., 2010; Yin et al., 2012). PCP phenotypes are also found in mice mutant for and mutant embryos fail to Talabostat mesylate polarize intercalation events within the plane of the tissue, affecting both apical and basal cell behaviors, while Lp mutant embryos maintain tissue polarity but are deficient in apical neighbor exchange, thus affecting only apical cell behavior. Observation of these unique cell behavior phenotypes has allowed us to functionally individual mechanisms in both the apical and basal domains of intercalating epithelial cells. Results The mouse neural plate undergoes convergent extension Eight hour time-lapse confocal movies were made of e8.0 mT/mG:ZP3 cre embryos in which every cell expresses membrane-targeted eGFP (mG). These time-lapse series focus on the ventral neural plate beginning at approximately 2 to 4 somite stage (observe movie S1). To quantify the normal progress of neural CE, tissue shape changes were measured using distortion diagrams. Diagrams overlying wild Talabostat mesylate type (WT) neural plates undergo substantial elongation and modest narrowing (Fig. 1ACA), which is usually indicative of CE. The extent of CE was determined by measuring the switch in average anterior-posterior (AP) length and mediolateral (ML) width of distortion diagrams over Talabostat mesylate time. WT neural plates elongate by an average of 22.3% and narrow by an average of 7.7%, resulting in a 35.4% average increase in overall AP to ML ratio, or CE index (Fig. 1G,H). Open in a separate window Physique 1 The neural plate of e8 mouse embryos undergoes CE, which is usually reduced in Lp and Ptk7 mutant embryosA,C,E) Snapshots from eight hour live time-lapse movies of fluorescently labeled e8 mouse embryos. Distortion diagrams overlying neural plates symbolize changes in the relative position of cells over time. Anterior is up, scale bars are 25m. A, A) Wild type embryo (N= 12). C, C) Vangl2 Lp mutant embryo (N=4). E, E) Ptk7 mutant embryo (N=4). B,D,F) Images of whole e8 embryos, genotype indicated at left. Dotted lines represent length of AP axis, which is usually conspicuously shorter in Ptk7 mutants (F). Anterior is usually left. G) Graph summarizing the percent switch in AP/ML ratio of distortion diagrams overlying neural plates of each embryo type over approximately eight hours. Bars labeled with the same letter are not statistically different (Kruskal-Wallis, p .05). H) Graph summarizing the percent switch in the AP (vertical striped bars) and ML sizes (horizontal striped bars) of distortion diagrams overlying neural plates of each embryo type. All bars are means with SEM. See also Fig. S2; movie S1. Mouse neural tissue is usually highly proliferative, and oriented division FSCN1 may contribute to the overall elongation and shaping of the neural tube (Sausedo et al., 1997). We measured the orientation of both the division plane and final position of child cells relative to the ACP axis in dividing cells observed within four WT time-lapse movies. No bias in the orientation of either was observed (Fig. S1). It is conceivable, however, that oriented cell divisions Talabostat mesylate may play a more substantial role in neural elongation at later stages of development. Because our analysis encompasses neural plate morphogenesis only at early somite stages, we cannot exclude this possibility. Regardless of their orientations, in the mouse, cell cycles include growth and increase Talabostat mesylate the volume of the tissue. The amount of convergence observed (7.7%) is relatively modest compared with the amount of extension (22.3%), suggesting that elongation of the neural plate likely occurs by a combination of increased tissue volume and convergence, with the increase in volume being channeled into extension. Neural CE is usually disrupted in embryos mutant for Vangl2 and Ptk7 Embryos homozygous for mutations in or exhibit dramatic defects in axial elongation. Both are given birth to with severely shortened A/P body axes and exhibit craniorachischisis, a failure of the neural tube to close posterior to the midbrain (Greene et al., 1998; Lu et al., 2004). To determine how neural CE is usually affected by mutations in.