Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs

Mech Dev. 2012 Sep-Dec;129(9-12):255-62. doi: 10.1016/j.mod.2012.07.003. Epub 2012 Jul 25.

Abstract

The intervertebral discs, located between adjacent vertebrae, are required for stability of the spine and distributing mechanical load throughout the vertebral column. All cell types located in the middle regions of the discs, called nuclei pulposi, are derived from the embryonic notochord. Recently, it was shown that the hedgehog signaling pathway plays an essential role during formation of nuclei pulposi. However, during the time that nuclei pulposi are forming, Shh is expressed in both the notochord and the nearby floor plate. To determine the source of SHH protein sufficient for formation of nuclei pulposi we removed Shh from either the floor plate or the notochord using tamoxifen-inducible Cre alleles. Removal of Shh from the floor plate resulted in phenotypically normal intervertebral discs, indicating that Shh expression in this tissue is not required for disc patterning. In addition, embryos that lacked Shh in the floor plate had normal vertebral columns, demonstrating that Shh expression in the notochord is sufficient for pattering the entire vertebral column. Removal of Shh from the notochord resulted in the absence of Shh in the floor plate, loss of intervertebral discs and vertebral structures. These data indicate that Shh expression in the notochord is sufficient for patterning of the intervertebral discs and the vertebral column.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Body Patterning / drug effects
  • Body Patterning / genetics*
  • Female
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / genetics*
  • Hedgehog Proteins / metabolism
  • Intervertebral Disc / anatomy & histology
  • Intervertebral Disc / drug effects
  • Intervertebral Disc / growth & development*
  • Intervertebral Disc / metabolism
  • Male
  • Mice
  • Notochord / anatomy & histology
  • Notochord / drug effects
  • Notochord / growth & development*
  • Notochord / metabolism
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Tamoxifen / pharmacology

Substances

  • Hedgehog Proteins
  • Paired Box Transcription Factors
  • Shh protein, mouse
  • Tamoxifen
  • PAX1 transcription factor