β-catenin-driven binary cell fate decisions in animal development

Abstract

The Wnt/β-catenin pathway plays key roles during animal development. In several species, β-catenin is used in a reiterative manner to regulate cell fate diversification between daughter cells following division. This binary cell fate specification mechanism has been observed in animals that belong to very diverse phyla: the nematode Caenorhabditis elegans, the annelid Platynereis, and the ascidian Ciona. It may also play a role in the regulation of several stem cell lineages in vertebrates. While the molecular mechanism behind this binary cell fate switch is not fully understood, it appears that both secreted Wnt ligands and asymmetric cortical factors contribute to the generation of the difference in nuclear β-catenin levels between daughter cells. β-Catenin then cooperates with lineage specific transcription factors to induce the expression of novel sets of transcription factors at each round of divisions, thereby diversifying cell fate. For further resources related to this article, please visit the WIREs website.

Figure 1

The Wnt/β‐catenin pathway. Simplified scheme of the Wnt/β‐catenin pathway. Only the components discussed in this review are presented. LRP, lipoprotein receptor‐related protein (a Frizzled coreceptor); Dsh, Dishevelled; CK1, casein kinase 1; GSK3, glycogen synthase kinase 3; APC, adenomatous polyposis coli; β‐cat, β‐catenin.

Figure 2

Role of β‐catenin in axis specification and reiterative binary cell fate specification in metazoans. Phylogenetic tree summarizing the role of Wnt signaling in axis specification or binary cell fate specification, as indicated by the key. The question mark for binary cell fate specification in vertebrates illustrates the potential role of β‐catenin in several vertebrate stem cell lineages (see text for details).

Figure 3

Reiterative β‐catenin asymmetries during C. elegans development. (a) Early embryo of C. elegans. (b) Example of a terminal neuronal lineage in the late embryo. (c) Early larva of C. elegans. The stem cell‐like seam cells are located on each side of the larva. The seam cells are presented just after one of their divisions, the anterior daughter ‘β‐catenin OFF’ will differentiate, while the posterior daughter ‘β‐catenin ON’ will remain a seam cell. (d) Typical succession of divisions in a seam cell lineage of the C. elegans larva. Ant., anterior; Post., posterior.

Figure 4

Reiterative β‐catenin asymmetries during Platynereis development. (a) Early embryo of Platynereis. (b) Typical succession of divisions in the early embryo of Platynereis. An., animal; Veg., vegetal.

Figure 5

Reiterative β‐catenin asymmetries during Ciona development. (a) Succession of divisions in the Ciona embryo from the 8‐cell stage to the 32‐cell stage. Only cells of the anterior half of the embryo are presented (‘a’ and ‘A’ lineages). (b) Schematic representation of the binary decisions. Only divisions along the animal (an.)–vegetal (veg.) axis are presented (the 8‐ to 16‐cell stage division that is perpendicular to the animal–vegetal axis is omitted).

Figure 6

Generation of β‐catenin and TCF asymmetries in C. elegans. Model for the generation of the asymmetries of the β‐catenins SYS‐1 and WRM‐1, and of the TCF factor POP‐1 during asymmetric divisions. This model mostly derives from studies of the division of the EMS cell in the embryo and of the T cell in the larva.

Figure 7

Model for the integration of β‐catenin asymmetries into the gene regulatory network of C. elegans. (a) Model for the generation of novel regulatory states during two rounds of division. For details on the mechanism of transcriptional activation of target genes in anterior daughter cells by POP‐1 (?) see text and panel (b). (b) Transcriptional activation of target genes in Wnt ‘OFF’ (anterior) cells. This regulation can be either indirect (via the repression of a posterior repressor) or direct (via the formation of a POP‐1:REF‐2 protein complex).

Figure 8

Model for the integration of β‐catenin asymmetries into the gene regulatory network of Ciona. The regulations of the FoxD gene by TCF:β‐catenin and of the Fog gene by GATAa are direct. Whether the other regulations are direct remains to be determined.