Loss of procollagen IIA from the anterior mesendoderm disrupts the development of mouse embryonic forebrain

Dev Dyn. 2010 Sep;239(9):2319-29. doi: 10.1002/dvdy.22366.


Morphogenesis of the mammalian forebrain is influenced by the patterning activity of signals emanating from the anterior mesendoderm. In this study, we show that procollagen IIA (IIA), an isoform of the cartilage extracellular matrix protein encoded by an alternatively spliced transcript of Col2a1, is expressed in the prechordal plate and the anterior definitive endoderm. In the absence of IIA activity, the null mutants displayed a partially penetrant phenotype of loss of head tissues, holoprosencephaly, and loss of mid-facial structures, which is associated with reduced sonic hedgehog (Shh) expression in the prechordal mesoderm. Genetic interaction studies reveal that IIA function in forebrain and face development does not involve bone morphogenetic protein receptor 1A (BMPR1A)- or NODAL-mediated signaling activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning*
  • Bone Morphogenetic Protein Receptors, Type I / genetics
  • Bone Morphogenetic Protein Receptors, Type I / metabolism
  • Collagen Type II / genetics
  • Collagen Type II / metabolism*
  • Endoderm / metabolism*
  • Head / abnormalities
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Mesoderm / metabolism*
  • Mice
  • Mice, Knockout
  • Nodal Protein / metabolism
  • Procollagen / genetics
  • Procollagen / metabolism*
  • Prosencephalon / anatomy & histology
  • Prosencephalon / embryology*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • RNA, Messenger / metabolism
  • Signal Transduction / physiology


  • Col2a1 protein, mouse
  • Collagen Type II
  • Hedgehog Proteins
  • Nodal Protein
  • Procollagen
  • Protein Isoforms
  • RNA, Messenger
  • Shh protein, mouse
  • Bmpr1a protein, mouse
  • Bone Morphogenetic Protein Receptors, Type I