دورية أكاديمية

Simultaneous deletion of Prdm1 and Vsx2 enhancers in the retina alters photoreceptor and bipolar cell fate specification, yet differs from deleting both genes.

التفاصيل البيبلوغرافية
العنوان: Simultaneous deletion of Prdm1 and Vsx2 enhancers in the retina alters photoreceptor and bipolar cell fate specification, yet differs from deleting both genes.
المؤلفون: Goodson NB; Sue Anschutz Rodgers Eye Center, Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Neuroscience Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Kaufman MA; Sue Anschutz Rodgers Eye Center, Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Cell Biology, Stem Cells, and Development Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Park KU; Sue Anschutz Rodgers Eye Center, Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Brzezinski JA 4th; Sue Anschutz Rodgers Eye Center, Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA Joseph.Brzezinski@cuanschutz.edu.
المصدر: Development (Cambridge, England) [Development] 2020 Jul 03; Vol. 147 (13). Date of Electronic Publication: 2020 Jul 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Company Of Biologists Limited Country of Publication: England NLM ID: 8701744 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-9129 (Electronic) Linking ISSN: 09501991 NLM ISO Abbreviation: Development Subsets: MEDLINE
أسماء مطبوعة: Publication: Cambridge Eng : Company Of Biologists Limited
Original Publication: [Cambridge] : Company of Biologists, [c1987-
مواضيع طبية MeSH: Homeodomain Proteins/*metabolism , Photoreceptor Cells/*metabolism , Positive Regulatory Domain I-Binding Factor 1/*metabolism , Retina/*metabolism , Transcription Factors/*metabolism, Animals ; CRISPR-Cas Systems/genetics ; CRISPR-Cas Systems/physiology ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Homeodomain Proteins/genetics ; Mice ; Otx Transcription Factors/genetics ; Otx Transcription Factors/metabolism ; Positive Regulatory Domain I-Binding Factor 1/genetics ; Retina/cytology ; Retinal Bipolar Cells/cytology ; Retinal Bipolar Cells/metabolism ; Transcription Factors/genetics
مستخلص: The transcription factor OTX2 is required for photoreceptor and bipolar cell formation in the retina. It directly activates the transcription factors Prdm1 and Vsx2 through cell type-specific enhancers. PRDM1 and VSX2 work in opposition, such that PRDM1 promotes photoreceptor fate and VSX2 bipolar cell fate. To determine how OTX2+ cell fates are regulated in mice, we deleted Prdm1 and Vsx2 or their cell type-specific enhancers simultaneously using a CRISPR/Cas9 in vivo retina electroporation strategy. Double gene or enhancer targeting effectively removed PRDM1 and VSX2 protein expression. However, double enhancer targeting favored bipolar fate outcomes, whereas double gene targeting favored photoreceptor fate. Both conditions generated excess amacrine cells. Combined, these fate changes suggest that photoreceptors are a default fate outcome in OTX2+ cells and that VSX2 must be present in a narrow temporal window to drive bipolar cell formation. Prdm1 and Vsx2 also appear to redundantly restrict the competence of OTX2+ cells, preventing amacrine cell formation. By taking a combinatorial deletion approach of both coding sequences and enhancers, our work provides new insights into the complex regulatory mechanisms that control cell fate choice.
Competing Interests: Competing interestsThe authors declare no competing or financial interests.
(© 2020. Published by The Company of Biologists Ltd.)
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معلومات مُعتمدة: R01 EY024272 United States EY NEI NIH HHS; T32 NS099042 United States NS NINDS NIH HHS; TL1 TR002533 United States TR NCATS NIH HHS
فهرسة مساهمة: Keywords: Bipolar; Enhancers; Mouse; Photoreceptors; Prdm1; Retina; Vsx2
المشرفين على المادة: 0 (Homeodomain Proteins)
0 (Otx Transcription Factors)
0 (Prdm1 protein, mouse)
0 (Transcription Factors)
0 (Vsx2 protein, mouse)
EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1)
تواريخ الأحداث: Date Created: 20200617 Date Completed: 20210409 Latest Revision: 20231125
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10666920
DOI: 10.1242/dev.190272
PMID: 32541005
قاعدة البيانات: MEDLINE
الوصف
تدمد:1477-9129
DOI:10.1242/dev.190272