TY  - JOUR
A1  - Demal, Till Joscha
A1  - Heise, Melina
A1  - Reiz, Benedikt
A1  - Dogra, Deepika
A1  - Braenne, Ingrid
A1  - Reichenspurner, Hermann
A1  - Männer, Jörg
A1  - Aherrahrou, Zouhair
A1  - Schunkert, Heribert
A1  - Erdmann, Jeanette
A1  - Abdelilah-Seyfried, Salim
T1  - A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A
JF  - Scientific reports
N2  - The genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329.2:c.1328 G > A (p.R443H)] which encodes a predicted deleterious variant of BMPR1A. This mutation co-segregates with a linkage region on chromosome 1 that associates with the emergence of severe CHDs including Ebstein’s anomaly, atrioventricular septal defect, and others. We show that the continuous overexpression of the zebrafish homologous mutation bmpr1aap.R438H within endocardium causes a reduced AV valve area, a downregulation of Wnt/ß-catenin signalling at the AV canal, and growth of additional tissue mass in adult zebrafish hearts. This finding opens the possibility of testing genetic interactions between BMPR1A and other candidate genes within linkage region 1 which may provide a first step towards unravelling more complex genetic patterns in cardiovascular disease aetiology.
Y1  - 2019
U6  - https://doi.org/10.1038/s41598-019-39648-7
SN  - 2045-2322
VL  - 9
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Lombardo, Verónica A.
A1  - Heise, Melina
A1  - Moghtadaei, Motahareh
A1  - Bornhorst, Dorothee
A1  - Männer, Jörg
A1  - Abdelilah-Seyfried, Salim
T1  - Morphogenetic control of zebrafish cardiac looping by Bmp signaling
JF  - Development : Company of Biologists
N2  - Cardiac looping is an essential and highly conserved morphogenetic process that places the different regions of the developing vertebrate heart tube into proximity of their final topographical positions. High-resolution 4D live imaging of mosaically labelled cardiomyocytes reveals distinct cardiomyocyte behaviors that contribute to the deformation of the entire heart tube. Cardiomyocytes acquire a conical cell shape, which is most pronounced at the superior wall of the atrioventricular canal and contributes to S-shaped bending. Torsional deformation close to the outflow tract contributes to a torque-like winding of the entire heart tube between its two poles. Anisotropic growth of cardiomyocytes based on their positions reinforces S-shaping of the heart. During cardiac looping, bone morphogenetic protein pathway signaling is strongest at the future superior wall of the atrioventricular canal. Upon pharmacological or genetic inhibition of bone morphogenetic protein signaling, myocardial cells at the superior wall of the atrioventricular canal maintain cuboidal cell shapes and S-shaped bending is impaired. This description of cellular rearrangements and cardiac looping regulation may also be relevant for understanding the etiology of human congenital heart defects.
KW  - BMP
KW  - Wnt
KW  - Cardiac looping
KW  - Hemodynamics
KW  - Zebrafish
Y1  - 2019
U6  - https://doi.org/10.1242/dev.180091
SN  - 0950-1991
SN  - 1477-9129
VL  - 146
IS  - 22
PB  - The Company of Biologists Ltd
CY  - Cambridge
ER  -