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PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF
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نویسنده
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raviv s. ,bharti k. ,rencus-lazar s. ,cohen-tayar y. ,schyr r. ,evantal n. ,meshorer e. ,zilberberg a. ,idelson m. ,reubinoff b. ,grebe r. ,rosin-arbesfeld r. ,lauderdale j. ,lutty g. ,arnheiter h. ,ashery-padan r.
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منبع
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plos genetics - 2014 - دوره : 10 - شماره : 5
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چکیده
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During organogenesis,pax6 is required for establishment of various progenitor subtypes within the central nervous system,eye and pancreas. pax6 expression is maintained in a variety of cell types within each organ,although its role in each lineage and how it acquires cell-specific activity remain elusive. herein,we aimed to determine the roles and the hierarchical organization of the pax6-dependent gene regulatory network during the differentiation of the retinal pigmented epithelium (rpe). somatic mutagenesis of pax6 in the differentiating rpe revealed that pax6 functions in a feed-forward regulatory loop with mitf during onset of melanogenesis. pax6 both controls the expression of an rpe isoform of mitf and synergizes with mitf to activate expression of genes involved in pigment biogenesis. this study exemplifies how one kernel gene pivotal in organ formation accomplishes a lineage-specific role during terminal differentiation of a single lineage.
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آدرس
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department of human molecular genetics and biochemistry,tel aviv university,tel aviv, Israel, unit on ocular and stem cell translational research,national eye institute,national institutes of health,bethesda,md, United States, department of human molecular genetics and biochemistry,tel aviv university,tel aviv, Israel, department of human molecular genetics and biochemistry,tel aviv university,tel aviv, Israel, department of genetics,the institute of life sciences,the hebrew university of jerusalem,jerusalem, Israel, department of genetics,the institute of life sciences,the hebrew university of jerusalem,jerusalem, Israel, department of genetics,the institute of life sciences,the hebrew university of jerusalem,jerusalem, Israel, department of clinical microbiology and immunology,sackler school of medicine,tel aviv university,tel aviv, Israel, the hadassah human embryonic stem cell research center,the goldyne savad institute of gene therapy and department of gynecology,hadassah-hebrew university medical center,jerusalem, Israel, the hadassah human embryonic stem cell research center,the goldyne savad institute of gene therapy and department of gynecology,hadassah-hebrew university medical center,jerusalem, Israel, wilmer ophthalmological institute,the johns hopkins university,school of medicine,baltimore,md, United States, department of clinical microbiology and immunology,sackler school of medicine,tel aviv university,tel aviv, Israel, department of cellular biology,the university of georgia,athens,ga, United States, wilmer ophthalmological institute,the johns hopkins university,school of medicine,baltimore,md, United States, mammalian development section,national institute of neurological disorders and stroke,national institute of health,bethesda,md, United States, department of human molecular genetics and biochemistry,tel aviv university,tel aviv, Israel
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Authors
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