Further Development 4.1: Sorting Out the Early Embryo

Cell-to-Cell Communication: Mechanisms of Morphogenesis

In vertebrate embryos, several major cadherin types have been identified. For example, E-cadherin is expressed on all early mammalian embryonic cells, even at the zygote stage. In the zebrafish embryo, E-cadherin is needed for the formation and migration of the epiblast as a sheet of cells during gastrulation. Loss of E-cadherin in the half-baked zebrafish mutant results in a failure of deep epiblast cells to move radially into the more superficial epiblast layer, an in vivo cell sorting process known as radial intercalation that helps power epiboly (spreading) of the epiblast during gastrulation (Figure 4.1; see also Chapter 11 and Kane et al. 2005). Later in development, this E-cadherin is restricted to epithelial tissues of embryos and adults.

In mammals, P-cadherin is found predominantly on the placenta, where it helps the placenta stick to the uterus (Nose and Takeichi 1986; Kadokawa et al. 1989). N-cadherin becomes highly expressed on the cells of the developing central nervous system (Hatta and Takeichi 1986), while R-cadherin is critical in retina formation (Babb et al. 2005). A class of cadherins called protocadherins (Sano et al. 1993) lacks the attachment to the actin cytoskeleton through catenins. Expressing similar protocadherins is an important means of keeping migrating epithelial cells together, and expressing dissimilar protocadherins is an important way of separating tissues (as when the axial mesoderm forming the notochord separates from the surrounding paraxial mesoderm that will form somites; see Chapter 17).

Figure 1 E-cadherin is required for epiboly in zebrafish. (A) Wild-type embryos (right), and embryos heterozygous (center) and homozygous (left) for the E-cadherin mutation called half-baked. During normal gastrulation, cells merge into a thinner but more expansive epiblast layer that envelops the entire yolk (the red arrowhead points to the location of final yolk enclosure in the wild-type). E-cadherin mutants fail to complete epiboly, which is most severely impaired in the homozygous mutant (red lines denote the leading edge of epiblast). (B) Schematic of radial intercalating cell movements in the zebrafish epiblast over time during gastrulation. Cells move toward the superficial enveloping layer in relationship to increasing expression of E-cadherin. E-cadherin is expressed at higher levels in the more superficial layers of the epiblast, including the enveloping layer, and it is this differential expression (and consequently differential adhesion) that powers the radial movement of deep cells to the periphery. EVL, enveloping layer; HB, hypoblast; YSL, yolk syncytial layer. (Data and images based on D. A. Kane et al. 2005. Development 132: 1105–1116, courtesy of R. Warga.)

Literature Cited

Babb, S. G., S. M. Kotradi, B. Shah, C. Chiappini-Williamson, L. N. Bell, G. Schmeiser, E. Chen, Q. Liu and J. A. Marrs. 2005. Zebrafish R-cadherin (Cdh4) controls visual system development and differentiation. Dev. Dyn. 233: 930–945.
PubMed Link

Hatta, K. and M. Takeichi. 1986. Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature 320: 447–449.
PubMed Link

Kadokawa, Y., I. Fuketa, A. Nose, M. Takeichi and N. Nakatsuji. 1989. Expression of E- and P-cadherin in mouse embryos and uteri during the periimplantation period. Dev. Growth Diff. 31: 23–30.

Kane, D. A., K. N. McFarland and R. M. Warga. 2005. Mutations in half baked/E-cadherin block cell behaviors that are necessary for teleost epiboly. Development 132: 1105–1116.
PubMed Link

Nose, A. and M. Takeichi. 1986. A novel cadherin adhesion molecule: Its expression patterns associated with implantation and organogenesis of mouse embryos. J. Cell Biol. 103: 2649–2658.
PubMed Link

Sano, K., H. Tanihara, R. L. Heimark, S. Obata, M. Davidson, T. St John, S. Taketani and S. Suzuki. 1993. Protocadherins: A family of cadherin-related molecules in central nervous system. EMBO J. 12: 2249–2256.
PubMed Link

All the material on this website is protected by copyright. It may not be reproduced in any form without permission from the copyright holder.

Back to top