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ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling,Determining Human Brain Size
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نویسنده
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kadir r. ,harel t. ,markus b. ,perez y. ,bakhrat a. ,cohen i. ,volodarsky m. ,feintsein-linial m. ,chervinski e. ,zlotogora j. ,sivan s. ,birnbaum r.y. ,abdu u. ,shalev s. ,birk o.s.
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منبع
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plos genetics - 2016 - دوره : 12 - شماره : 3
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چکیده
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Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume,with fewer neurons in the cortex of the developing brain due to premature transition between symmetrical and asymmetrical cellular division of the neuronal stem cell layer during neurogenesis. we now show through linkage analysis and whole exome sequencing,that a dominant mutation in alfy,encoding an autophagy scaffold protein,causes human primary microcephaly. we demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume,recapitulating the disease phenotype. moreover,eye-specific expression of human mutant alfy causes rough eye phenotype. in molecular terms,we demonstrate that normally alfy attenuates the canonical wnt signaling pathway via autophagy-dependent removal specifically of aggregates of dvl3 and not of dvl1 or dvl2. thus,autophagic attenuation of wnt signaling through removal of dvl3 aggregates by alfy acts in determining human brain size. © 2016 kadir et al.
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آدرس
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the morris kahn laboratory of human genetics,national institute for biotechnology in the negev,ben gurion university,beer sheva, Israel, the morris kahn laboratory of human genetics,national institute for biotechnology in the negev,ben gurion university,beer sheva, Israel, the morris kahn laboratory of human genetics,national institute for biotechnology in the negev,ben gurion university,beer sheva, Israel, the morris kahn laboratory of human genetics,national institute for biotechnology in the negev,ben gurion university,beer sheva, Israel, department of life sciences,ben gurion university,beer sheva, Israel, the morris kahn laboratory of human genetics,national institute for biotechnology in the negev,ben gurion university,beer sheva, Israel, the morris kahn laboratory of human genetics,national institute for biotechnology in the negev,ben gurion university,beer sheva, Israel, the morris kahn laboratory of human genetics,national institute for biotechnology in the negev,ben gurion university,beer sheva, Israel, genetics institute,haemek medical center,afula, Israel, department of community genetics,public health services,ministry of health,jerusalem, Israel, the morris kahn laboratory of human genetics,national institute for biotechnology in the negev,ben gurion university,beer sheva, Israel, department of life sciences,ben gurion university,beer sheva, Israel, department of life sciences,ben gurion university,beer sheva, Israel, genetics institute,haemek medical center,afula, Israel, the morris kahn laboratory of human genetics,national institute for biotechnology in the negev,ben gurion university,beer sheva,israel,genetics institute,soroka university medical center,ben gurion university,beer sheva, Israel
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Authors
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