Editors' ChoiceDevelopment

Separated in Time and Space

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Sci. Signal.  07 Feb 2012:
Vol. 5, Issue 210, pp. ec45
DOI: 10.1126/scisignal.2002925

Specification of the endoderm and mesoderm in animals is a multistep process in which cells are first specified as endomesoderm (alternately referred to as mesendoderm), then this tissue is further segregated into separate endoderm and mesoderm populations. In sea urchin embryos, nuclear localization of the Wnt signaling effector β-catenin establishes an early endoderm identity in cells neighboring the descendants of the micromeres, which are the most ventrally located cells of the embryo, and induces expression of the gene encoding the Notch ligand Delta in the micromere descendants. Cells closest to the micromere descendants become mesoderm, whereas cells farther away adopt an endodermal fate. Sethi et al. report that this Wnt signaling event is the first in a series of interactions between the Notch and Wnt signaling pathways that separate the endomesoderm into endoderm and mesoderm. The homeobox transcription factor Hox11/13b induces the expression of endoderm-specific genes, and Notch signaling repressed the expression of hox11/13b in the cells closest to the micromere descendants, thus specifying these cells as mesoderm. Hox11/13b was also required for expression of wnt1, so Notch signaling also restricted production of this Wnt ligand to the cells that will ultimately become endoderm. Wnt1 was required in the endoderm for maintenance of Hox11/13b and other endodermal markers. The authors propose that the absence of Wnt signaling reinforced mesodermal identity by reducing the nuclear accumulation of β-catenin, thus enabling the β-catenin binding partner TCF to repress expression of the endoderm marker foxa. Notch signaling also promotes expression of the mitogen-activated protein kinase NLK in sea urchins, which, in other systems, can promote nuclear export of TCF. The authors observed that TCF later disappeared from mesodermal nuclei, thus reducing the Wnt response in these cells to further reinforce the mesodermal fate. The temporal and spatial restriction of Notch and Wnt signaling thus specifies and reinforces endodermal and mesodermal identity in the early sea urchin embryo.

A. J. Sethi, R. M. Wikramanayake, R. C. Angerer, R. C. Range, L. M. Angerer, Sequential signaling crosstalk regulates endomesoderm segregation in sea urchin embryos. Science 335, 590–593 (2012). [Abstract] [Full Text]

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