Nkx2-5 and Sarcospan genetically interact in the development of the muscular ventricular septum of the heart.

Autor: Panzer AA; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Regmi SD; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Cormier D; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Danzo MT; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Chen ID; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Winston JB; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Hutchinson AK; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Salm D; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Schulkey CE; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Cochran RS; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Wilson DB; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA.; Department of Developmental Biology, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA., Jay PY; Department of Pediatrics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA.; Department of Genetics, Washington University School of Medicine, Box 8208 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Apr 13; Vol. 7, pp. 46438. Date of Electronic Publication: 2017 Apr 13.
DOI: 10.1038/srep46438
Abstrakt: The muscular ventricular septum separates the flow of oxygenated and de-oxygenated blood in air-breathing vertebrates. Defects within it, termed muscular ventricular septal defects (VSDs), are common, yet less is known about how they arise than rarer heart defects. Mutations of the cardiac transcription factor NKX2-5 cause cardiac malformations, including muscular VSDs. We describe here a genetic interaction between Nkx2-5 and Sarcospan (Sspn) that affects the risk of muscular VSD in mice. Sspn encodes a protein in the dystrophin-glycoprotein complex. Sspn knockout (Sspn KO ) mice do not have heart defects, but Nkx2-5 +/- /Sspn KO mutants have a higher incidence of muscular VSD than Nkx2-5 +/- mice. Myofibers in the ventricular septum follow a stereotypical pattern that is disrupted around a muscular VSD. Subendocardial myofibers normally run in parallel along the left ventricular outflow tract, but in the Nkx2-5 +/- /Sspn KO mutant they commonly deviate into the septum even in the absence of a muscular VSD. Thus, Nkx2-5 and Sspn act in a pathway that affects the alignment of myofibers during the development of the ventricular septum. The malalignment may be a consequence of a defect in the coalescence of trabeculae into the developing ventricular septum, which has been hypothesized to be the mechanistic basis of muscular VSDs.
Databáze: MEDLINE
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