Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation
- Department of Molecular Biosciences, University of Texas, United States
- Department of Chemistry, University of Texas, United States
- Department of Chemistry and Physics, Augusta University, Georgia
Figures
Figure 1 with 3 supplements
Vertices bounding shortening v-junctions are physically asymmetric and display heterogeneous fluid and glass-like dynamics.
(A) A four cell T1 transition with mediolaterally (ML)-aligned ‘v-junctions’ (red) and anterior-posterior (A/P) aligned t-junctions (orange) indicated. (B) Frames from time-lapse showing vertex …
Figure 1—figure supplement 1
Schematics of Xenopus development.
(A) Cartoon depiction of Xenopus gastrulation, tadpole axis elongation, and the consequence of convergent extension defects. Here the mesoderm in the dorsal marginal zone (DMZ) involutes and …
Figure 1—figure supplement 2
Mean squared displacement measured from multiple frames of reference.
Appendix, Section 1. (A) Schematic showing how vertex MSD was measured from the lab frame of reference. Here the coordinate plane was set with the upper left corner of the image as (x,y)(0,0) and …
Figure 1—figure supplement 3
Extended analysis of vertex glass-like dynamics.
(A) Probability distribution of active (red) and passive (blue) vertex displacements, referred to as the van Hove function (see Equation 4 in Appendix Section 2), shows distinct non-Gaussian …
Figure 2 with 1 supplement
A new vertex model incorporating local mechanical heterogeneity recapitulates the fine-scale dynamics of junction shortening observed in vivo.
(A) Sketch of v- junction shortening with elements of the model overlain. Active (red) and passive (blue) vertex movements are affected by a piston modulating the dynamic rest length. The vertices …
Figure 2—figure supplement 1
Extended analysis comparing in vivo and in silico junction dynamics.
(A) C. Normalized relative change in length, , versus time for shortening mediolateral cell-cell junctions during CE. 21 individual junctions from 20 embryos are analyzed. and are the …
Figure 3
Patterns of transverse vertex fluctuations reveal mechanical heterogeneity of active and passive vertices in vivo.
(A) Schematic of transverse fluctuations in the vertex position perpendicular to the direction of junction shortening; traverse movements are extracted using the transverse 'hop' function, which is …
Figure 4 with 2 supplements
Cadherin cis-clustering correlates with vertex movements and mirrors asymmetric vertex dynamics.
(A) C-cadherin (Cdh3) cis-clustering; trans-dimers form across opposing cell membranes (gray); lateral cis interactions drive clustering. (B) Frames from time-lapse of Cdh3-GFP; white arrows …
Figure 4—figure supplement 1
Extended analysis pertaining to cdh3 clustering and actin next to junctions (Appendix, Section 16).
(A) Schematic showing how actin was measured next to active and passive vertices at shortening v-junctions. (B) Graph showing junction length and actin intensities over time for a single shortening …
Figure 4—figure supplement 2
Source data for spatial correlation of Cdh3 intensity fluctuations reveal extreme heterogeneity in cluster size.
(A-J) Individual (time frame by frame) spatial correlation vs distance curves selecting for shortening events from 10 distinct cell-cell junctions that undergo successful junction shortening …
Figure 5 with 1 supplement
Cdh3 cis-clustering is required for convergent extension but not homeostatic tissue integrity.
(A) Mutations used to inhibit cadherin cis-clustering. (B) Cdh3-GFP clustering in a control embryo. (C) Cis-clusters absent after re-expression of cisMut-Cdh3-GFP. (D) Mean spatial autocorrelation …
Figure 5—figure supplement 1
Cdh3 knockdown.
(A) Embryos were injected with Cdh3-MO and membrane-BFP in a single dorsal blastomere at the four-cell stage resulting in mosaic depletion of Cdh3. Here, immuno-staining for Cdh3 shows that the …
Figure 6
Cdh3 cis-clustering is required for heterogeneous junction mechanics.
(A) Image of polarized, elongated control Xenopus mesoderm cells. Blue = mediolateral (ML); yellow = anterior-posterior (AP). (B) Stage-matched cells after depletion of endogenous Cdh3 and …
Figure 7 with 1 supplement
PCP is required for cdh3 cis-clustering and heterogeneous junction mechanics.
(A) Cartoon of polarized core PCP protein localization. (B) Still image of Cdh3-GFP after expression of dominant negative Dvl2 (Xdd1). (C) Spatial autocorrelation of Cdh3 intensity fluctuations for …
Figure 7—figure supplement 1
Extended analysis of cadherin clustering for the cis-mutant, rescue, and Xdd1.
(A) Spatial autocorrelation of Cdh3 intensity fluctuations for wild type (60 frames, obtained from 10 embryos) and Cdh3-rescue (58 frames, obtained from 4 embryos). The characteristic correlation …
