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Int J Dev Biol
2021 Jan 01;654-5-6:227-233. doi: 10.1387/ijdb.200231ja.
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Establishing embryonic territories in the context of Wnt signaling.
Velloso I
,
Maia LA
,
Amado NG
,
Reis AH
,
He X
,
Abreu JG
.
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This review highlights the work that my research group has been developing, together with international collaborators, during the last decade. Since we were able to establish the Xenopus laevis experimental model in Brazil, we have been focused on understanding early embryonic patterns regarding neural induction and axes establishment. In this context, the Wnt pathway appears as a major player and has been much explored by us and other research groups. Here, we chose to review three published works which we consider to be landmarks within the course of our research and also within the history of modern findings regarding neural induction and patterning. We intend to show how our series of discoveries, when painted together, tells a story that covers crucial developmental windows of early differentiation paths of anterior neural tissue: 1. establishing the headorganizer in contrast to the trunkorganizer in the early gastrula; 2. deciding between neural ectoderm and epidermisectoderm at the blastula/gastrula stages, and 3. the gathering of prechordal unique properties in the late gastrula/early neurula.
Figure 1: Schematic representation of the Wnt/β-catenin signaling pathway and different ways it can be inhibited.
(A) Wnt ON, See text for details (B) Wnt OFF: Extracellular Wnt antagonists such as secreted frizzled-related proteins (sFRP1-5) and Cerberus sequester Wnt ligands in extracellular spaces. Secreted protein Dickkopf1 (DKK1) competitively binds to Wnt ligand-receptor LRP5/6, which leads to a ternary complex formation with the Kremen receptor (Kre), a transmembrane protein, followed by endocytosis and degradation of the LRP5/6 receptor. Notum, a Wnt deacylase, hydrolyzes the Wnt palmitoleoylate adduct extracellularly, resulting in inactivated Wnt proteins that form oxidized oligomers incapable of receptor binding. Tiki-1, a transmembrane protein with proteolytic activity, cleaves a peptide from the N-terminal part of Wnt proteins. This causes the formation of oligomers of Wnt proteins that are inactive in signal transduction. Tiki-1 can also act in the endoplasmic reticulum (ER)/Golgi, wherein it inactivates Wnt before it is secreted into the extracellular space through secretory vesicles.
Figure 2. Xenopus laevis stages.
A) 2-cell, B) 4-cell, C) 8-cell, D) 16-cell, E) 32-cell, F-H) stage 8-9 blastula stages, I) Stage 10,5 gastrula, J) Stage 11,5 early neurula stage, K) Stage 12, L) stage 13, M) stage 22, N) stage 28 tailbud, O) stage 35, P) stage 42 tadpole. A-H) animal pole view, I-J) vegetal pole view, K-L) dorsal view, M-P, lateral view. Courtesy by Karla Almeida Coburn from her master dissertation, 2005.
Figure 3. A) Short scheme of Tiki1 loss-of-function experiments on Spemann Organizer and HeadOrganizer markers, B) Short scheme of Notum loss-of-function experiments on neural plate formation, C) Short scheme on the Methyl-β-cyclodextrin (MβCD) treatment and its phenotype. See text for details.
