دورية أكاديمية
Nkx genes establish second heart field cardiomyocyte progenitors at the arterial pole and pattern the venous pole through Isl1 repression.
| العنوان: | Nkx genes establish second heart field cardiomyocyte progenitors at the arterial pole and pattern the venous pole through Isl1 repression. |
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| المؤلفون: | Colombo S; Division of Cardiology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA., de Sena-Tomás C; Division of Cardiology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA., George V; Division of Cardiology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA., Werdich AA; Brigham and Women's Hospital/Harvard Medical School, Cardiovascular Division, 75 Francis Street, Thorn 11, Boston, MA 02115, USA., Kapur S; Brigham and Women's Hospital/Harvard Medical School, Cardiovascular Division, 75 Francis Street, Thorn 11, Boston, MA 02115, USA., MacRae CA; Brigham and Women's Hospital/Harvard Medical School, Cardiovascular Division, 75 Francis Street, Thorn 11, Boston, MA 02115, USA., Targoff KL; Division of Cardiology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA kl284@columbia.edu. |
| المصدر: | Development (Cambridge, England) [Development] 2018 Feb 05; Vol. 145 (3). Date of Electronic Publication: 2018 Feb 05. |
| 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: | Heart/*embryology , Homeobox Protein Nkx-2.5/*genetics , Homeodomain Proteins/*genetics , LIM-Homeodomain Proteins/*genetics , Myoblasts, Cardiac/*cytology , Myoblasts, Cardiac/*metabolism , Transcription Factors/*genetics , Zebrafish Proteins/*genetics, Animals ; Animals, Genetically Modified ; Body Patterning/genetics ; Cell Differentiation ; Cell Proliferation ; Gene Expression Regulation, Developmental ; Heart Defects, Congenital/embryology ; Heart Defects, Congenital/genetics ; Humans ; Mutation |
| مستخلص: | NKX2-5 is the most commonly mutated gene associated with human congenital heart defects (CHDs), with a predilection for cardiac pole abnormalities. This homeodomain transcription factor is a central regulator of cardiac development and is expressed in both the first and second heart fields (FHF and SHF). We have previously revealed essential functions of nkx2.5 and nkx2.7 , two Nkx2-5 homologs expressed in zebrafish cardiomyocytes, in maintaining ventricular identity. However, the differential roles of these genes in the specific subpopulations of the anterior (aSHF) and posterior (pSHF) SHFs have yet to be fully defined. Here, we show that Nkx genes regulate aSHF and pSHF progenitors through independent mechanisms. We demonstrate that Nkx genes restrict proliferation of aSHF progenitors in the outflow tract, delimit the number of pSHF progenitors at the venous pole and pattern the sinoatrial node acting through Isl1 repression. Moreover, optical mapping highlights the requirement for Nkx gene dose in establishing electrophysiological chamber identity and in integrating the physiological connectivity of FHF and SHF cardiomyocytes. Ultimately, our results may shed light on the discrete errors responsible for NKX2-5 -dependent human CHDs of the cardiac outflow and inflow tracts. Competing Interests: Competing interestsS.C. is currently a consultant for Pairnomix, but the work presented in this paper has no connection with this company. (© 2018. Published by The Company of Biologists Ltd.) |
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| معلومات مُعتمدة: | R24 OD017870 United States OD NIH HHS; K08 HL088002 United States HL NHLBI NIH HHS; K12 HD043389 United States HD NICHD NIH HHS; R01 HL131438 United States HL NHLBI NIH HHS; R00 HL112724 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: Arterial pole; Second heart field; Venous pole; Zebrafish; nkx2.5; nkx2.7 |
| المشرفين على المادة: | 0 (Homeobox Protein Nkx-2.5) 0 (Homeodomain Proteins) 0 (LIM-Homeodomain Proteins) 0 (Nkx2.5 protein, zebrafish) 0 (Nkx2.7 protein, zebrafish) 0 (Transcription Factors) 0 (Zebrafish Proteins) 0 (insulin gene enhancer binding protein Isl-1) |
| تواريخ الأحداث: | Date Created: 20180124 Date Completed: 20180409 Latest Revision: 20190201 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5818010 |
| DOI: | 10.1242/dev.161497 |
| PMID: | 29361575 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1477-9129 |
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| DOI: | 10.1242/dev.161497 |