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Mouse models of holoprosencephaly.
Monica Hayhurst1, Susan K McConnell
1Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Current Opinion in Neurology
|March 20, 2003
Summary
Holoprosencephaly (HPE) is a common human forebrain development anomaly. Mouse models reveal gene disruptions in Sonic hedgehog and Nodal pathways contribute to HPE, aiding understanding of human brain development.
Area of Science:
- Developmental biology
- Neuroscience
- Genetics
Background:
- Holoprosencephaly (HPE) is the most common forebrain development anomaly in humans.
- HPE pathogenesis involves the failure of cerebral hemispheres to separate during early embryonic development.
Purpose of the Study:
- To review experimental mouse models of HPE.
- To examine gene disruptions known to cause HPE in humans.
Main Methods:
- Review of existing literature on HPE.
- Analysis of genetically altered mouse models with disrupted HPE-associated genes.
- Focus on genes within Sonic hedgehog (SHH) and Nodal signaling pathways.
Main Results:
- Mutations in seven genes are linked to HPE, with three affecting the SHH pathway and two affecting Nodal ligands.
- SHH and Nodal pathways are crucial for neural patterning and development.
- Genetically modified mice show HPE phenotypes when SHH and Nodal pathway members are mutated.
Conclusions:
- Mouse models offer a framework for understanding human HPE and may identify new candidate genes.
- Further research is needed to clarify how ventral patterning molecules disrupt dorsal cerebral hemisphere formation.