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An in vitro model o...
An in vitro model of lissencephaly : expanding the role of DCX during neurogenesis
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- Shahsavani, M (author)
- Karolinska Institutet
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- Pronk, R J (author)
- Karolinska Institutet
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Falk, R (author)
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Lam, M (author)
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- Moslem, M (author)
- Karolinska Institutet
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Linker, S B (author)
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Salma, J (author)
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Day, K (author)
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- Schuster, Jens (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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Anderlid, B-M (author)
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- Dahl, Niklas (author)
- Uppsala universitet,Medicinsk genetik och genomik
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Gage, F H (author)
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- Falk, A (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-09-19
- 2018
- English.
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In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 23:7, s. 1674-1684
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Lissencephaly comprises a spectrum of brain malformations due to impaired neuronal migration in the developing cerebral cortex. Classical lissencephaly is characterized by smooth cerebral surface and cortical thickening that result in seizures, severe neurological impairment and developmental delay. Mutations in the X-chromosomal gene DCX, encoding doublecortin, is the main cause of classical lissencephaly. Much of our knowledge about DCX-associated lissencephaly comes from post-mortem analyses of patient's brains, mainly since animal models with DCX mutations do not mimic the disease. In the absence of relevant animal models and patient brain specimens, we took advantage of induced pluripotent stem cell (iPSC) technology to model the disease. We established human iPSCs from two males with mutated DCX and classical lissencephaly including smooth brain and abnormal cortical morphology. The disease was recapitulated by differentiation of iPSC into neural cells followed by expression profiling and dissection of DCX-associated functions. Here we show that neural stem cells, with absent or reduced DCX protein expression, exhibit impaired migration, delayed differentiation and deficient neurite formation. Hence, the patient-derived iPSCs and neural stem cells provide a system to further unravel the functions of DCX in normal development and disease.Molecular Psychiatry advance online publication, 19 September 2017; doi:10.1038/mp.2017.175.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Shahsavani, M
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Pronk, R J
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Falk, R
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Lam, M
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Moslem, M
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Linker, S B
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show more...
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Salma, J
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Day, K
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Schuster, Jens
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Anderlid, B-M
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Dahl, Niklas
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Gage, F H
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Falk, A
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Molecular Psychi ...
- By the university
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Uppsala University
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Karolinska Institutet