Genetic interaction between Wnt7a and Lrp6 during patterning of dorsal and posterior structures of the mouse limb

Dev Dyn. 2005 Jun;233(2):368-72. doi: 10.1002/dvdy.20437.

Abstract

Wnt7a and the Wnt coreceptor Lrp6 are both required for development of posterior digits and dorsal structures of the limb. We report that Lrp6 null mice lack Lmx1b expression in the distal mesenchyme, as previously described for Wnt7a mutants. The loss of Lmx1b expression in Wnt7a-/-Lrp6+/- double mutants did not differ from that in Wnt7a-/- mice. These data suggest that Wnt7a acts through Lrp6 to regulate Lmx1b expression during dorsal specification. The loss of posterior skeletal elements in the Wnt7a-/-Lrp6+/- double mutant was much more severe than in Wnt7a-/- mice, suggesting that the Wnt7a-/- limb is protected by the action of other Lrp6 ligands. The data are consistent with the view that Wnt7a acts through Lrp6 and the canonical Wnt signaling pathway during dorsal and posterior limb development in the mouse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Extremities / embryology*
  • Gene Expression Regulation, Developmental / genetics*
  • Genotype
  • Homeodomain Proteins / metabolism
  • LDL-Receptor Related Proteins / deficiency
  • LDL-Receptor Related Proteins / genetics*
  • LDL-Receptor Related Proteins / metabolism
  • LIM-Homeodomain Proteins
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Mice
  • Mice, Knockout
  • Mutation / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Skin / embryology*
  • Skin / metabolism*
  • Transcription Factors / metabolism
  • Wnt Proteins

Substances

  • Homeodomain Proteins
  • LDL-Receptor Related Proteins
  • LIM homeobox transcription factor 1 beta
  • LIM-Homeodomain Proteins
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Lrp6 protein, mouse
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Wnt Proteins
  • Wnt7a protein, mouse