Cdc42 deficiency causes Sonic hedgehog-independent holoprosencephaly

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چکیده

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Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly.

Holoprosencephaly (HPE), a human developmental brain defect, usually is also associated with varying degrees of midline facial dysmorphism. Heterozygous mutations in the Sonic hedgehog (SHH) gene are the most common genetic lesions associated with HPE, and loss of Shh function in the mouse produces cyclopia and alobar forebrain development. The N-terminal domain (ShhNp) of Sonic hedgehog protei...

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The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly.

Holoprosencephaly (HPE) is a common developmental anomaly of the human forebrain and midface where the cerebral hemispheres fail to separate into distinct left and right halves. We have previously reported haploinsufficiency for Sonic Hedgehog ( SHH ) as a cause for HPE. We have now performed mutational analysis of the complete coding region and intron-exon junctions of the SHH gene in 344 unre...

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Sonic hedgehog

Are there related proteins? Lots. In mammals, Sonic is related to two other hedgehogs: Indian and Desert. When expressed appropriately, the three proteins can substitute for one another but they do have unique functions: Desert hedgehog is needed for spermatogenesis and Indian hedgehog regulates cartilage differentiation. In the zebrafish, Sonic is related to Tiggywinkle hedgehog — which is tho...

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Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog.

Holoprosencephaly (HPE) is a clinically heterogeneous developmental anomaly affecting the CNS and face, in which the embryonic forebrain fails to divide into distinct halves. Numerous genetic loci and environmental factors are implicated in HPE, but mutation in the sonic hedgehog (Shh) gene is an established cause in both humans and mice. As growth arrest-specific 1 (Gas1) encodes a membrane gl...

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Ectopic sonic hedgehog signaling impairs telencephalic dorsal midline development: implication for human holoprosencephaly.

Holoprosencephaly (HPE) is the most common developmental anomaly of the human forebrain, and in its severe form, the cerebral hemispheres fail to completely separate into two distinct halves. Although disruption of ventral forebrain induction is thought to underlie most HPE cases, a subset of HPE patients exhibits preferential dysgenesis of forebrain dorsal midline structures with unknown etiol...

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ژورنال

عنوان ژورنال: Proceedings of the National Academy of Sciences

سال: 2006

ISSN: 0027-8424,1091-6490

DOI: 10.1073/pnas.0603533103