J Cell Biol
September 29, 2014;
Getting to know your neighbor: cell polarization in early embryos.
Polarization of early embryos along cell contact patterns--referred to in this paper as radial polarization--provides a foundation for the initial cell fate decisions and morphogenetic movements of embryogenesis. Although polarity can be established through distinct upstream mechanisms in Caenorhabditis elegans, Xenopus laevis, and mouse embryos, in each species, it results in the restriction of PAR polarity proteins to contact-free surfaces of blastomeres. In turn, PAR proteins influence cell fates by affecting signaling pathways, such as Hippo and Wnt, and regulate morphogenetic movements by directing cytoskeletal asymmetries.
J Cell Biol
[+] show captions
References [+] :
Figure 1. Blastomeres and epithelial cells. (A and B) A generic zygote, morula stage embryos containing unpolarized then polarized blastomeres (A), and a blastocyst stage embryo containing polarized epithelial cells (B) illustrate the concepts of blastomere polarization and subsequent epithelial cell formation. (A) The zygote undergoes cleavage to first produce unpolarized blastomeres. Blastomeres subsequently develop radial polarity by differentiating their contacted (red) and contact-free (green) surfaces. (B) Polarized blastomeres eventually develop into fully polarized epithelial cells. Cell surface domains of generic mammalian epithelial cells, along with representative polarity and junction proteins found within these domains, are shown. The developmental stage when blastomeres polarize radially and the time required for cells to transition to mature epithelia vary considerably among species, as exemplified by the three model systems that are the focus of this review. Crb, Crumbs; Lgl, Lethal giant larvae.
Figure 2. A/P and radial polarity in the C. elegans embryo. (A) The zygote polarizes along its A/P axis, distributing PAR proteins to distinct anterior and posterior domains. PAR-3, PAR-6, and PKC-3/aPKC enrich at the anterior cortex, whereas PAR-1 and PAR-2 concentrate at the posterior cortex. (B) During the four-cell stage (an eight-cell embryo is shown), the axis of PAR protein asymmetry switches from A/P to contacted and contact free as the embryo polarizes radially. PAR-3, PAR-6, and PKC-3 are found at contact-free surfaces of cells, whereas PAR-1 and PAR-2 are found at contacted surfaces. The single germline precursor cell (asterisk) does not polarize radially and instead retains the A/P asymmetry of PAR proteins seen in the zygote. (C) Radial polarization is initiated and maintained by a contact-induced asymmetry in Rho GTPase activity. The RhoGAP PAC-1 binds to the cortex adjacent to contact sites, where it is predicted to locally inactivate CDC-42 (CDC-42–GDP). Active CDC-42 (CDC-42–GTP) is thus restricted to contact-free surfaces where it recruits PAR-3, PAR-6, and PKC-3.
Figure 3. Polarization of Xenopus embryos during cleavage. (A) Deposition of new (basolateral) membrane during cleavage. A dividing one-cell embryo is shown, with membrane inherited from the egg and new membrane trafficked to the furrow. In the inset, concentrations of furrow MTs are seen at the base of the ingressing cleavage furrow. Separate astral MTs are also present. (B) Formation of superficial (outer) and deep (inner) cell layers. All cells have a superficial surface at the 32-cell stage. Asymmetric divisions over the next several cleavage cycles produce a population of deep cells that lie in the interior of the embryo, as shown in a 128-cell embryo. Membranes of superficial cells are polarized, with aPKC and Par6B at apical surfaces and Par1 and Lrp6 at basolateral surfaces. Notch signaling, which is inhibited by Par1, is high in superficial cells (dark shading) and low in deep cells (light shading). Lrp6 asymmetry also creates differences in Wnt signaling between superficial and deep cells (not depicted).
Figure 4. Compaction and radial polarization in the eight-cell mouse embryo. During the eight-cell stage, rounded nonpolar blastomeres compact with one another and also polarize along their radial axis. A 16-cell embryo is shown on the right. Par3, Par6B, and aPKC are restricted to contact-free surfaces, whereas Par1/EMK1 and E-cadherin are found at cell contacts.
Figure 5. Hippo signaling in outer and inner cells of the mouse embryo. (A) Hippo signaling patterns inner and outer cell fates in the morula. Yap is found in the cytoplasm in inner cells (where Hippo signaling is active) and in the nucleus in outer cells. In outer cells, Yap together with Tead4 (not depicted) is required for the expression of Cdx2, a transcription factor that promotes TE differentiation. Yap asymmetry is directed by Amot, which is found all around the surfaces of inner cells but only at contact-free surfaces of outer cells. Amot and the interacting protein E-cadherin colocalize only in inner cells. (B) Model for polarity and adhesion-mediated Hippo pathway asymmetry in outer and inner cells. In outer cells, nonphosphorylated Amot interacts with apical actin, Nf2, and Lats, sequestering Lats and preventing Hippo pathway activity. Consequently, Yap is nuclear. In inner cells, phosphorylated Amot complexes with Nf2 and Lats at AJs, leading to Hippo pathway activity and restriction of Yap to the cytoplasm. The model is based on Hirate and Sasaki (2014). P, phosphorylation.
Aceto, Interaction of PAR-6 with CDC-42 is required for maintenance but not establishment of PAR asymmetry in C. elegans. 2006, Pubmed