Mutations in the BMP pathway in mice support the existence of two molecular classes of holoprosencephaly

Development. 2007 Nov;134(21):3789-94. doi: 10.1242/dev.004325. Epub 2007 Oct 3.


Holoprosencephaly (HPE) is a devastating forebrain abnormality with a range of morphological defects characterized by loss of midline tissue. In the telencephalon, the embryonic precursor of the cerebral hemispheres, specialized cell types form a midline that separates the hemispheres. In the present study, deletion of the BMP receptor genes, Bmpr1b and Bmpr1a, in the mouse telencephalon results in a loss of all dorsal midline cell types without affecting the specification of cortical and ventral precursors. In the holoprosencephalic Shh(-/-) mutant, by contrast, ventral patterning is disrupted, whereas the dorsal midline initially forms. This suggests that two separate developmental mechanisms can underlie the ontogeny of HPE. The Bmpr1a;Bmpr1b mutant provides a model for a subclass of HPE in humans: midline inter-hemispheric HPE.

Publication types

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

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors, Type I / deficiency
  • Bone Morphogenetic Protein Receptors, Type I / genetics
  • Bone Morphogenetic Protein Receptors, Type I / metabolism
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Brain / embryology
  • Brain / metabolism
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Holoprosencephaly / embryology
  • Holoprosencephaly / genetics
  • Holoprosencephaly / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation / genetics*
  • Phenotype
  • Signal Transduction*


  • Bone Morphogenetic Proteins
  • Hedgehog Proteins
  • Shh protein, mouse
  • Bone Morphogenetic Protein Receptors, Type I