Research

Molecular Mechanisms of Early Patterning

The early patterning of animal embryos is entrained by the polarized distribution of regulatory molecules (proteins and mRNAs) in the unfertilized egg. One highly conserved system of molecular polarity involves components of the canonical Wnt signaling pathway. In many metazoans, the proteolytic degradation of ß-catenin, an important transcriptional effector of Wnt signaling, is polarized along the early embryonic axis. The stabilization of ß-catenin on one side of the early embryo results in the local activation of target genes that specify the endomesoderm and its associated signaling centers. An important regulator of this pathway is dishevelled (Dsh), a protein that protects ß-catenin from proteolytic degradation. During oogenesis, Dsh is directed to the vegetal cortex via specific targeting motifs located near the N-terminus of the protein. During cleavage, Dsh is inherited by vegetal blastomeres and stabilizes ß-catenin selectively in these cells. Our current work is aimed at: 1) further elucidating the molecular basis of the intracellular targeting of Dsh, 2) uncovering additional mechanisms that act in parallel with Dsh to stabilize ß-catenin in vegetal blastomeres, and 3) understanding the differential responses of vegetal blastomeres to ß-catenin.

Dishevelled (Dsh) protein is targeted to the vegetal pole of the egg. Confocal image of a zygote injected with mRNA encoding GFP-tagged Dsh. After two hours, newly synthesized Dsh-GFP is localized at the vegetal cortex.

Polarized degradation of beta-catenin along the axis of the early embryo. This time-lapse movie was generated from confocal image stacks of a cleavage-stage embryo injected with mRNA encoding beta-catenin-GFP. The GFP-tagged protein is degraded selectively in animal cells. In vegetal cells, beta-catenin is stable and activates GRNs that underlie mesoderm and endoderm development (from Weitzel et al., 2004).

Relevant Papers

Khor JM, Guerrero-Santoro J, Ettensohn CA. Molecular compartmentalization in a syncytium: restricted mobility of proteins within the sea urchin skeletogenic mesenchyme. Development. 2023 Nov 15;150(22):dev201804. doi: 10.1242/dev.201804. Epub 2023 Nov 27. PMID: 37902109. PDF

Chess MM, Douglas W, Saunders J, Ettensohn CA. Genome-wide identification and spatiotemporal expression analysis of cadherin superfamily members in echinoderms. Evodevo. 2023 Dec 20;14(1):15. doi: 10.1186/s13227-023-00219-7. PMID: 38124068; PMCID: PMC10734073. PDF

Ettensohn CA. Embryonic polarity: Focusing on Dishevelled. Curr Biol. 2021 Dec 20;31(24):R1582-R1585. doi: 10.1016/j.cub.2021.10.060. PMID: 34932969. PDF

Stamateris, R. E., Rafiq, K., and Ettensohn, C. A. (2010). The expression and distribution of Wnt and Wnt receptor mRNAs during early sea urchin development. Gene Expr. Patterns 10: 60-64. PDF

Leonard, J. and Ettensohn, C. A. (2007). Analysis of dishevelled localization and function in the early sea urchin embryo. Dev. Biol. 306: 50-65. PDF

Ettensohn, C. A. (2006). The emergence of pattern in embryogenesis: Regulation of beta-catenin localization during early sea urchin development. STKE Perspective, Science 361: pe48. PDF

Weitzel, H. E., Illies, M. R., Byrum, C. A., Xu, R., Wikramanayake, A. H., and Ettensohn, C. A. (2004). Differential stability of beta-catenin along the animal-vegetal axis of the sea urchin embryo mediated by dishevelled. Development 131: 2947-2956. PDF