Hedgehog pathway - Problems with the hedgehog pathway
5 important questions on Hedgehog pathway - Problems with the hedgehog pathway
Which molecule is needed for the hedghog pathway? And which syndrom do you get when you have a fold in this molecule formation.
Formed in all cells, but particullarly in hepatocyten.
Also essential to formation bile acid and vit D and steroid hormones.
There are 8 steps in the formation of cholesterol => every step can lead to a problem.
SLOS (Smith Lemli Opitz Syndrom)
- microcephaly
- Cleft palate
- dysmorph face
- hangend of laagstaand ooglid = ptosis
- callosal agenesis
- brain defect
- polydactyly
- ambigous genitals
- cryptorchidism (niet ingedaalde teeltballen)
What is the mutation for SLOS?
What are the hedgehog-cholesterol phenotypes?
- CNS disorders: MR, Dorsal-ventral patterning defects (callosal agenesis, HPE), neural tube closure defects
- Limb / skeletal affections: brachydactyly, broad thumbs/toes, polydactyly, syndactyly, rhizo/mesomelia, ectopic calcifications
- Skin disorders: hyperkeratosis, skin atrophy, pigmentation, alopecia.
- Craniofacial anomalies: craniosynostosis, microcephaly, macrocephaly, hypertelorism (ogen uit elkaar), cleft palate
- Urogenital disorders: cryptorchidism, hypogonadism, ambiguous genitals
- (susceptability to) tumors: chondroma, basal cell carcinoma, prostate- and pancreatic cancer, medulloblastoma
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What are results of a mutation in patched? PTCH.
SMO stimulates the Gli proteins, transcription factors. Which are important for brain, lung and limb development. What are the results of mutations or overexpression?
Overexpression => cancer
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