Reduction in E-cadherin expression fosters migration of Xenopus laevis primordial germ cells

Abstract

The transition from passive to active migration of primordial germ cells in Xenopus embryos correlates with a reduction in overall adhesion to surrounding endodermal cells as well as with reduced E-cadherin expression. Single cell force spectroscopy, in which cells are brought into brief contact with a gold surface functionalized with E-cadherin constructs, allows for a quantitative estimate of functional E-cadherin molecules on the cell surface. The adhesion force between migratory PGCs and the cadherin-coated surface was almost identical to cells where E-cadherin was knocked down by morpholino oligonucleotides (180 pN). In contrast, non-migratory PGCs display significantly higher adhesion forces (270 pN) on E-cadherin functionalised surfaces. On the basis of these observations, we propose that migration of PGCs in Xenopus embryos is regulated via modulation of E-cadherin expression levels, allowing these cells to move more freely if the level of E-cadherin is reduced.

Dual Role of Cell-Cell Adhesion In Tumor Suppression and Proliferation Due to Collective Mechanosensing

“…2a). While N = 12, 000 cells on day 7.5 at f ad = 1.75 × 10 −4 µN/µm 2 , for higher values (3 × 10 −4 µN/µm 2 ), the tumor consists of only 4, 000 at the same t. The surprising non-monotonic dependence of cell numbers, N, on f ad , is qualitatively consistent with some recent experiments [36,43], as we discuss below. The non-monotonic proliferation behavior becomes pronounced beginning at t = 5τ min (see Fig.…”

“…The mechanism, identified here, is related to the pressure dependent feedback on growth [15] whose effectiveness is controlled by cell-cell adhesion strength, f ad . Plausible Connection To Experiments: We mention two experiments, which provide quantitative support to our conclusion: (1) Maintenance of appropriate E-cadherin expression is required for normal cell development in several species such as Drosophila, zebrafish and mouse [43,55]. In order to make quantitative connec- tions between our findings and experiments, we consider a study on how the proliferation capacity of primordial germ cells (PGCs) depend on cell-cell adhesion.…”

The Central Role of Cadherins in Gonad Development, Reproduction, and Fertility

“…The level of E-cadherin expression decreases during the active PGCs migration through the endoderm in the hindgut. A decline in E-cadherin expression leads to PGCs individualization and dispersion, and it lowers their affinity to the surrounding endodermal cells (which express a high level of E-cadherin) facilitating migration [43]. Such a transient decline of E-cadherin expression in the migrating PGCs was also reported in zebrafish [44] and Xenopus [45].…”

Non-junctional role of Cadherin3 in cell migration and contact inhibition of locomotion via domain-dependent, opposing regulation of Rac1

“…The expression level of the Cdh3 and Cdh3 mutant proteins was measured in the same protocol of western blot used for measuring Rac1 activity. Protein extracts were as described previously 76 . After transfer, blots were probed with mouse anti-cdh3 (C-cadherin; Clone 6B6, Developmental Studies Hybridoma Bank, dilution 1:300), mouse anti-cdh1 (E-cadherin; Clone 5D3, Developmental Studies Hybridoma Bank, dilution 1:300), anti-Myc (Clone 9E10, Sigma-Aldrich, dilution 1:1,000), and rabbit anti-ɣTubulin (T3320, Sigma-Aldrich, dilution 1:3,000).…”