Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells

Research output: Contribution to journalArticlepeer-review


  • Dilek Colak
  • Tetsuji Mori
  • Monika S. Brill
  • Alexander Pfeifer
  • Sven Falk
  • Chuxia Deng
  • Christine Mummery
  • Lukas Sommer
  • Magdalena Götz

Colleges, School and Institutes

External organisations

  • Helmholtz Zentrum München
  • Kansai Medical University
  • University of Munich
  • University of Bonn
  • Universität Zürich
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • Hubrecht Laboratory KNAW (Netherlands Institute for Developmental Biology)
  • Institute for Stem Cell Research


In the mammalian brain, neurogenesis continues only in few regions of the forebrain. The molecular signals governing neurogenesis in these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active in adult neural stem cells and is crucial to initiate the neurogenic lineage in the adult mouse subependymal zone. Conditional deletion of Smad4 in adult neural stem cells severely impairs neurogenesis, and this is phenocopied by infusion of Noggin, an extracellular antagonist of BMP. Smad4 deletion in stem, but not progenitor cells, as well as Noggin infusion lead to an increased number of Olig2-expressing progeny that migrate to the corpus callosum and differentiate into oligodendrocytes. Transplantation experiments further verified the cell-autonomous nature of this phenotype. Thus, BMP-mediated signaling via Smad4 is required to initiate neurogenesis from adult neural stem cells and suppress the alternative fate of oligodendrogliogenesis.


Original languageEnglish
Pages (from-to)434-446
Number of pages13
JournalJournal of Neuroscience
Issue number2
Publication statusPublished - 9 Jan 2008


  • Dlx2, Neural stem cells, Neurogenesis, Olig2, Oligodendrocytes, Transplantation

ASJC Scopus subject areas