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Downstream of β-catenin: A positive feedback loop between Goosecoid and Nodals in Spemann’s organizer

Yagmur Azbazdar, Edward M. De Robertis

Revista con revisión por paresAfirmaciones fuertes, leer con cuidado

En palabras de los autores

We report on the role of the homeobox gene goosecoid ( gsc ) within an epistatic pathway that mediates body axis formation in Xenopus . Embryos depleted of β-catenin form exclusively ventral structures and lack all traces of axial structures. Microinjection of gsc mRNA rescues an entire body axis with head and trunk-tail. This remarkable activity is shared with the homeobox gene siamois ( sia ) and growth factors of the Nodal family. Using a Gsc antisense morpholino, we showed that dorsalization by Xenopus nodal-related 6 mRNA has a strong requirement for Gsc in β-catenin depleted embryos. These experiments uncovered a positive feedback loop between Gsc and Nodal that is required downstream of β-catenin for the maintenance of dorsal and anterior tissues during gastrulation in endomesoderm. The Gsc-Xnr feedback loop leads to the expression of Spemann organizer genes that antagonize signals from ventral tissues. Similarly, rescue of β-catenin depletion by murine β-catenin mRNA also has a requirement for Gsc. Although gsc is a gene conserved throughout the animal kingdom during evolution, its loss-of-function during mouse gastrulation has only very weak phenotypic effects; perhaps the redundancy described here in Xenopus might be part of the explanation. The functional pathway defined here is self-organizing and robust as required to form a perfect embryo time after time.

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Apareció: sábado, 26 de septiembre. Proceedings of the National Academy of Sciences. Revista con revisión por pares.

DOI: 10.1073/pnas.2610127123