BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo

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BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. / Chuva De Sousa Lopes, Susana M.; Roelen, Bernard A. J.; Monteiro, Rui M.; Emmens, Roul; Lin, Herbert Y.; Li, En; Lawson, Kirstie A.; Mummery, Christine L.

In: Genes and Development, Vol. 18, No. 15, 01.08.2004, p. 1838-1849.

Research output: Contribution to journalArticle

Harvard

Chuva De Sousa Lopes, SM, Roelen, BAJ, Monteiro, RM, Emmens, R, Lin, HY, Li, E, Lawson, KA & Mummery, CL 2004, 'BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo', Genes and Development, vol. 18, no. 15, pp. 1838-1849. https://doi.org/10.1101/gad.294004

APA

Chuva De Sousa Lopes, S. M., Roelen, B. A. J., Monteiro, R. M., Emmens, R., Lin, H. Y., Li, E., Lawson, K. A., & Mummery, C. L. (2004). BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes and Development, 18(15), 1838-1849. https://doi.org/10.1101/gad.294004

Vancouver

Author

Chuva De Sousa Lopes, Susana M. ; Roelen, Bernard A. J. ; Monteiro, Rui M. ; Emmens, Roul ; Lin, Herbert Y. ; Li, En ; Lawson, Kirstie A. ; Mummery, Christine L. / BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. In: Genes and Development. 2004 ; Vol. 18, No. 15. pp. 1838-1849.

Bibtex

@article{7ea3abab470245ce8c545a66ba2f874a,
title = "BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo",
abstract = "Deletion of various bone morphogenetic proteins (BMPs) and their downstream Smads in mice have clearly shown that BMP signaling is essential for the formation of primordial germ cells (PGCs). However, the molecular mechanism through which this takes place is still unclear. Here, we demonstrate that BMP4 produced in the extraembryonic ectoderm signals through ALK2, a type I BMP receptor, in the visceral endoderm (VE) to induce formation of PGCs from the epiblast. Firstly, embryonic day 5.5-6.0 (E5.5-E6.0) embryos cultured on fibronectin formed PGCs in the presence of VE, but not in its absence. Secondly, Alk2-deficient embryos completely lacked PGCs and the heterozygotes had reduced numbers, resembling Bmp4-deficient phenotypes. Thirdly, expression of constitutively active ALK2 in the VE, but not in the epiblast, was sufficient to rescue the PGC phenotype in Bmp4-deficient embryos. In addition, we show that the requirement for the VE at E5.5-E6.0 can be replaced by culturing embryos stripped of VE on STO cells, indicating that STO cells provide or transduce signals necessary for PGC formation that are normally transmitted by the VE. We propose a model in which direct signaling to proximal epiblast is supplemented by an obligatory indirect BMP-dependent signal via the VE.",
keywords = "ALK2, BMP signaling, Embryo, Mouse, Primordial germ cells, Visceral endoderm",
author = "{Chuva De Sousa Lopes}, {Susana M.} and Roelen, {Bernard A. J.} and Monteiro, {Rui M.} and Roul Emmens and Lin, {Herbert Y.} and En Li and Lawson, {Kirstie A.} and Mummery, {Christine L.}",
year = "2004",
month = aug,
day = "1",
doi = "10.1101/gad.294004",
language = "English",
volume = "18",
pages = "1838--1849",
journal = "Genes & Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "15",

}

RIS

TY - JOUR

T1 - BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo

AU - Chuva De Sousa Lopes, Susana M.

AU - Roelen, Bernard A. J.

AU - Monteiro, Rui M.

AU - Emmens, Roul

AU - Lin, Herbert Y.

AU - Li, En

AU - Lawson, Kirstie A.

AU - Mummery, Christine L.

PY - 2004/8/1

Y1 - 2004/8/1

N2 - Deletion of various bone morphogenetic proteins (BMPs) and their downstream Smads in mice have clearly shown that BMP signaling is essential for the formation of primordial germ cells (PGCs). However, the molecular mechanism through which this takes place is still unclear. Here, we demonstrate that BMP4 produced in the extraembryonic ectoderm signals through ALK2, a type I BMP receptor, in the visceral endoderm (VE) to induce formation of PGCs from the epiblast. Firstly, embryonic day 5.5-6.0 (E5.5-E6.0) embryos cultured on fibronectin formed PGCs in the presence of VE, but not in its absence. Secondly, Alk2-deficient embryos completely lacked PGCs and the heterozygotes had reduced numbers, resembling Bmp4-deficient phenotypes. Thirdly, expression of constitutively active ALK2 in the VE, but not in the epiblast, was sufficient to rescue the PGC phenotype in Bmp4-deficient embryos. In addition, we show that the requirement for the VE at E5.5-E6.0 can be replaced by culturing embryos stripped of VE on STO cells, indicating that STO cells provide or transduce signals necessary for PGC formation that are normally transmitted by the VE. We propose a model in which direct signaling to proximal epiblast is supplemented by an obligatory indirect BMP-dependent signal via the VE.

AB - Deletion of various bone morphogenetic proteins (BMPs) and their downstream Smads in mice have clearly shown that BMP signaling is essential for the formation of primordial germ cells (PGCs). However, the molecular mechanism through which this takes place is still unclear. Here, we demonstrate that BMP4 produced in the extraembryonic ectoderm signals through ALK2, a type I BMP receptor, in the visceral endoderm (VE) to induce formation of PGCs from the epiblast. Firstly, embryonic day 5.5-6.0 (E5.5-E6.0) embryos cultured on fibronectin formed PGCs in the presence of VE, but not in its absence. Secondly, Alk2-deficient embryos completely lacked PGCs and the heterozygotes had reduced numbers, resembling Bmp4-deficient phenotypes. Thirdly, expression of constitutively active ALK2 in the VE, but not in the epiblast, was sufficient to rescue the PGC phenotype in Bmp4-deficient embryos. In addition, we show that the requirement for the VE at E5.5-E6.0 can be replaced by culturing embryos stripped of VE on STO cells, indicating that STO cells provide or transduce signals necessary for PGC formation that are normally transmitted by the VE. We propose a model in which direct signaling to proximal epiblast is supplemented by an obligatory indirect BMP-dependent signal via the VE.

KW - ALK2

KW - BMP signaling

KW - Embryo

KW - Mouse

KW - Primordial germ cells

KW - Visceral endoderm

UR - http://www.scopus.com/inward/record.url?scp=3543127068&partnerID=8YFLogxK

U2 - 10.1101/gad.294004

DO - 10.1101/gad.294004

M3 - Article

C2 - 15289457

AN - SCOPUS:3543127068

VL - 18

SP - 1838

EP - 1849

JO - Genes & Development

JF - Genes & Development

SN - 0890-9369

IS - 15

ER -