The extracellular regulation of bone morphogenetic protein signaling

Umulis, David M.; O’Connor, Michael B.; Blair, Seth S.

doi:10.1242/dev.031534

Cited by 196 publications

(235 citation statements)

References 154 publications

(206 reference statements)

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“…A gradient of BMP signaling patterns the embryo in many species (15,20), and it has been proposed that Chordin facilitates the D-V flux of BMPs in a Tolloid-regulated way (8,9). However, the physical location of endogenous gradient-forming signaling components remains unknown.…”

Section: Discussionmentioning

confidence: 99%

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Chordin forms a self-organizing morphogen gradient in the extracellular space between ectoderm and mesoderm in the Xenopus embryo

Plouhinec

Zakin

Moriyama

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The vertebrate body plan follows stereotypical dorsal-ventral (D-V) tissue differentiation controlled by bone morphogenetic proteins (BMPs) and secreted BMP antagonists, such as Chordin. The three germ layers-ectoderm, mesoderm, and endoderm-are affected coordinately by the Chordin-BMP morphogen system. However, extracellular morphogen gradients of endogenous proteins have not been directly visualized in vertebrate embryos to date. In this study, we improved immunolocalization methods in Xenopus embryos and analyzed the distribution of endogenous Chordin using a specific antibody. Chordin protein secreted by the dorsal Spemann organizer was found to diffuse along a narrow region that separates the ectoderm from the anterior endoderm and mesoderm. This Fibronectin-rich extracellular matrix is called "Brachet's cleft" in the Xenopus gastrula and is present in all vertebrate embryos. Chordin protein formed a smooth gradient that encircled the embryo, reaching the ventral-most Brachet cleft. Depletion with morpholino oligos showed that this extracellular gradient was regulated by the Chordin protease Tolloid and its inhibitor Sizzled. The Chordin gradient, as well as the BMP signaling gradient, was self-regulating and, importantly, was able to rescale in dorsal half-embryos. Transplantation of Spemann organizer tissue showed that Chordin diffused over long distances along this signaling highway between the ectoderm and mesoderm. Chordin protein must reach very high concentrations in this narrow region. We suggest that as ectoderm and mesoderm undergo morphogenetic movements during gastrulation, cells in both germ layers read their positional information coordinately from a single morphogen gradient located in Brachet's cleft.

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Section: Discussionmentioning

confidence: 99%

“…BMPs are secreted growth factors of the TGF-β superfamily, first discovered by Urist at the University of California, Los Angeles as bone-inducing factors in decalcified bone matrix extracts (7). A morphogen gradient of BMP signaling plays the key role in the differentiation of cells into dorsal-ventral (D-V) tissue types in vertebrates and Drosophila (8,9).…”

mentioning

confidence: 99%

Chordin forms a self-organizing morphogen gradient in the extracellular space between ectoderm and mesoderm in the Xenopus embryo

Plouhinec

Zakin

Moriyama

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…The induction of Blimp1 expression in the posterior side of the embryo is explained by the inhibition of BMP signaling in the anterior epiblast by antagonist factors (e.g., LEFTY1 against NODAL, DKK1 against WNT, and Cerberus-like [CER1] against BMP, etc.) that are emanated from the anterior visceral endoderm (AVE) (Umulis et al 2009). In Smad2 or Foxh1 mutants that fail to form AVE, Blimp1 expression becomes widespread in the epiblast.…”

Section: Signaling For Pgc Specificationmentioning

confidence: 99%

Primordial Germ Cells in Mice

Saitou

Yamaji

2012

Cold Spring Harbor Perspectives in Biology

352

307

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SUMMARYGerm cell development creates totipotency through genetic as well as epigenetic regulation of the genome function. Primordial germ cells (PGCs) are the first germ cell population established during development and are immediate precursors for both the oocytes and spermatogonia. We here summarize recent findings regarding the mechanism of PGC development in mice. We focus on the transcriptional and signaling mechanism for PGC specification, potential pluripotency, and epigenetic reprogramming in PGCs and strategies for the reconstitution of germ cell development using pluripotent stem cells in culture. Continued studies on germ cell development may lead to the generation of totipotency in vitro, which should have a profound influence on biological science as well as on medicine.

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“…The BMPs are members of the transforming growth factor-b (TGFb) family of secreted signaling molecules, and act through surface receptors and SMAD-type transcriptional regulator proteins. [4][5][6] BMP signaling is high in the epidermis and low in the neuroectoderm; the neural crest forms in the region of intermediate BMP signaling, which also corresponds to the most dorsolateral aspect of the neuroectoderm. In addition to BMP secretion, BMP signaling is controlled by secreted antagonists 7 as well as intracellular regulators.…”

Section: "Ectoderm and Endoderm Are Primary Germ Layers; They Were Thmentioning

confidence: 99%

Mechanisms driving neural crest induction and migration in the zebrafish andXenopus laevis

Klymkowsky

Rossi

Artinger

2010

Cell Adhesion & Migration

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The extracellular regulation of bone morphogenetic protein signaling

Cited by 196 publications

References 154 publications

Chordin forms a self-organizing morphogen gradient in the extracellular space between ectoderm and mesoderm in the Xenopus embryo

Chordin forms a self-organizing morphogen gradient in the extracellular space between ectoderm and mesoderm in the Xenopus embryo

Primordial Germ Cells in Mice

Mechanisms driving neural crest induction and migration in the zebrafish andXenopus laevis

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