Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse.
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.
Mukhopadhyay
M
M
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Shtrom
S
S
Rodriguez-Esteban
C
C
Chen
L
L
Tsukui
T
T
Gomer
L
L
Dorward
D W
DW
Glinka
A
A
Grinberg
A
A
Huang
S P
SP
Niehrs
C
C
Izpisúa Belmonte
J C
JC
Westphal
H
H
D000818:Animals; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000196:embryology; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000502:physiology* / Q000648:ultrastructure; D004627:Embryonic Induction / Q000502:physiology*; D005121:Extremities / Q000196:embryology* / Q000254:growth & development; D018390:Gene Targeting; D006257:Head / Q000196:embryology* / Q000254:growth & development; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C501128:dkk1b protein, zebrafish