Dickkopf1 Is Required for Embryonic Head Induction and Limb Morphogenesis in the Mouse

Mahua Mukhopadhyay, Svetlana Shtrom, Concepcion Rodriguez-Esteban, Lan Chen, Tohru Tsukui, Lauren Gomer, David W. Dorward, Andrei Glinka, Alexander Grinberg, Sing Ping Huang, Christof Niehrs, Juan Carlos Izpisua Belmonte, Heiner Westphal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

510 Scopus citations

Abstract

Dickkopf1 (Dkk1) is a secreted protein that acts as a Wnt inhibitor and, together with BMP inhibitors, is able to induce the formation of ectopic heads in Xenopus. Here, we show that Dkk1 null mutant embryos lack head structures anterior of the midbrain. Analysis of chimeric embryos implicates the requirement of Dkk1 in anterior axial mesendoderm but not in anterior visceral endoderm for head induction. In addition, mutant embryos show duplications and fusions of limb digits. Characterization of the limb phenotype strongly suggests a role for Dkk1 both in cell proliferation and in programmed cell death. Our data provide direct genetic evidence for the requirement of secreted Wnt antagonists during embryonic patterning and implicate Dkk1 as an essential inducer during anterior specification as well as a regulator during distal limb patterning.

Original languageEnglish (US)
Pages (from-to)423-434
Number of pages12
JournalDevelopmental Cell
Volume1
Issue number3
DOIs
StatePublished - Sep 1 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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