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

Research output: Contribution to journalArticlepeer-review


  • Susana M. Chuva De Sousa Lopes
  • Bernard A. J. Roelen
  • Roul Emmens
  • Herbert Y. Lin
  • En Li
  • Kirstie A. Lawson
  • Christine L. Mummery

Colleges, School and Institutes

External organisations

  • Utrecht University
  • Hubrecht Institute
  • Harvard Medical School
  • Wellman Center for Photomedicine
  • Novartis Institutes for BioMedical Research (NIBR)


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.


Original languageEnglish
Pages (from-to)1838-1849
Number of pages12
JournalGenes and Development
Issue number15
Publication statusPublished - 1 Aug 2004


  • ALK2, BMP signaling, Embryo, Mouse, Primordial germ cells, Visceral endoderm

ASJC Scopus subject areas