title: Mouse models of holoprosencephaly.
abstract: OBJECTIVE
  Holoprosencephaly (HPE) is the most common anomaly of forebrain development in humans. The pathogenesis of HPE results in a failure of the brain hemispheres to separate during early development. Here we review experimental models of HPE in which some of the genes known to cause HPE in humans have been disrupted in the mouse.
  
  
  RESULTS
  To date, mutations that cause HPE have been identified in seven genes. Three of these genes encode members of the Sonic hedgehog (SHH) signaling pathway, which regulates the development of ventral structures throughout the neuraxis. Two other HPE mutations affect signaling by Nodal ligands, which also play important roles in neural patterning. The roles of the two other known HPE genes are not yet clear. Analysis of genetically altered mice has revealed that mutations in other members of the SHH and Nodal signaling pathways also result in HPE phenotypes.
  
  
  CONCLUSIONS
  Studies of HPE in the mouse have provided a framework for understanding key developmental events in human brain development and may provide new candidate genes for human HPE. Despite this progress, fundamental mysteries remain about how molecules that pattern ventral brain regions ultimately disrupt the formation of the cerebral hemispheres in dorsal regions.
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Hayhurst
authors.forename: Susan K
authors.initials: SK
authors.lastname: McConnell
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005136:Eye Proteins; D053823:Hedgehog Proteins; D016142:Holoprosencephaly / Q000235:genetics* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055457:Nodal Protein; D009687:Nuclear Proteins; D016548:Prosencephalon / Q000002:abnormalities / Q000254:growth & development; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D055457:Nodal Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000097607:Homeobox Protein SIX3; C526007:NODAL protein, human; C526008:Nodal protein, mouse; C465570:Shh protein, mouse; C491812:ZIC2 protein, human; C491811:Zic2 protein, mouse