BMP signaling during bone pattern determination in the developing limb

Development. 1996 Nov;122(11):3557-66. doi: 10.1242/dev.122.11.3557.

Abstract

To examine the role of BMP signaling during limb pattern formation, we isolated chicken cDNAs encoding type I (BRK-1 and BRK-2) and type II (BRK-3) receptors for bone morphogenetic proteins. BRK-2 and BRK-3, which constitute dual-affinity signaling receptor complexes for BMPs, are co-expressed in condensing precartilaginous cells, while BRK-1 is weakly expressed in the limb mesenchyme. BRK-3 is also expressed in the apical ectodermal ridge and interdigital limb mesenchyme. BRK-2 is intensely expressed in the posterior-distal region of the limb bud. During digit duplication by implanting Sonic hedgehog-producing cells, BRK-2 expression is induced anteriorly in the new digit forming region as observed for BMP-2 and BMP-7 expression in the limb bud. Dominant-negative effects on BMP signaling were obtained by over-expressing kinase domain-deficient forms of the receptors. Chondrogenesis of limb mesenchymal cells is markedly inhibited by dominant-negative BRK-2 and BRK-3, but not by BRK-1. Although the bone pattern was not disturbed by expressing individual dominant-negative BRK independently, preferential distal and posterior limb truncations resulted from co-expressing the dominant-negative forms of BRK-2 and BRK-3 in the whole limb bud, thus providing evidence that BMPs are essential morphogenetic signals for limb bone patterning.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Morphogenetic Protein Receptors
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Protein Receptors, Type II
  • Bone Morphogenetic Proteins / physiology*
  • Bone and Bones / embryology
  • Cartilage / embryology
  • Cells, Cultured
  • Chickens
  • Extremities / embryology*
  • Genes, Dominant
  • Hedgehog Proteins
  • Molecular Sequence Data
  • Protein Serine-Threonine Kinases / physiology*
  • Proteins / physiology
  • Receptors, Cell Surface / physiology*
  • Receptors, Growth Factor / physiology*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Trans-Activators*

Substances

  • Bone Morphogenetic Proteins
  • Hedgehog Proteins
  • Proteins
  • Receptors, Cell Surface
  • Receptors, Growth Factor
  • Trans-Activators
  • Protein Serine-Threonine Kinases
  • Bone Morphogenetic Protein Receptors
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Protein Receptors, Type II

Associated data

  • GENBANK/AB006785