Abnormal anteroposterior and dorsoventral patterning of the limb bud in the absence of retinoids

Mech Dev. 1999 Mar;81(1-2):115-25. doi: 10.1016/s0925-4773(98)00231-7.


We describe here how the early limb bud of the quail embryo develops in the absence of retinoids, including retinoic acid. Retinoid-deficient embryos develop to about stage 20/21, thus allowing patterns of early gene activity in the limb bud to be readily examined. Genes representing different aspects of limb polarity were analysed. Concerning the anteroposterior axis, Hoxb-8 was up-regulated and its border was shifted anteriorly whereas shh and the mesodermal expression of bmp-2 were down-regulated in the absence of retinoids. Concerning the apical ectodermal genes, fgf-4 was down-regulated whereas fgf-8 and the ectodermal domain of bmp-2 were unaffected. Genes involved in dorsoventral polarity were all disrupted. Wnt-7a, normally confined to the dorsal ectoderm, was ectopically expressed in the ventral ectoderm and the corresponding dorsal mesodermal gene Lmx-1 spread into the ventral mesoderm. En-1 was partially or completely absent from the ventral ectoderm. These dorsoventral patterns of expression resemble those seen in En-1 knockout mouse limb buds. Overall, the patterns of gene expression are also similar to the Japanese limbless mutant. These experiments demonstrate that the retinoid-deficient embryo is a valuable tool for dissecting pathways of gene activity in the limb bud and reveal for the first time a role for retinoic acid in the organisation of the dorsoventral axis.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / metabolism
  • Coturnix / embryology*
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Homeodomain Proteins / metabolism
  • In Situ Hybridization
  • LIM-Homeodomain Proteins
  • Limb Buds / embryology*
  • Limb Buds / pathology
  • Ovum / metabolism*
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Retinoids / metabolism*
  • Trans-Activators*
  • Transcription Factors
  • Transforming Growth Factor beta*
  • Wnt Proteins


  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • EN1 protein, human
  • Fibroblast Growth Factor 4
  • HOXB8 protein, human
  • Hedgehog Proteins
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Lmx1a protein, mouse
  • Proteins
  • Proto-Oncogene Proteins
  • Retinoids
  • SHH protein, human
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Wnt7a protein, mouse
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors