Cardiovascular Patterning as Determined by Hemodynamic Forces and Blood Vessel Genetics.
BACKGROUND
Vascular patterning depends on coordinated timing of arteriovenous specification of endothelial cells and the concomitant hemodynamic forces supplied by the onset of cardiac function. Using a combination of 3D imaging by OPT and embryo registration techniques, we sought to identify structural differences between three different mouse models of cardiovascular perturbation.


RESULTS
Endoglin mutant mice shared a high degree of similarity to Mlc2a mutant mice, which have been shown to have a primary developmental heart defect causing secondary vessel remodeling failures. Dll4 mutant mice, which have well-characterized arterial blood vessel specification defects, showed distinct differences in vascular patterning when compared to the disruptions seen in Mlc2a-/- and Eng-/- models. While Mlc2a-/- and Eng-/- embryos exhibited significantly larger atria than wild-type, Dll4-/- embryos had significantly smaller hearts than wild-type, but this quantitative volume decrease was not limited to the developing atrium. Dll4-/- embryos also had atretic dorsal aortae and smaller trunks, suggesting that the cardiac abnormalities were secondary to primary arterial blood vessel specification defects.


CONCLUSIONS
The similarities in Eng-/- and Mlc2a-/- embryos suggest that Eng-/- mice may suffer from a primary heart developmental defect and secondary defects in vessel patterning, while defects in Dll4-/- embryos are consistent with primary defects in vessel patterning.
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; The Hospital For Sick Children, Toronto, Ontario, Canada.
Gregory A
GA
Anderson
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
Ryan S
RS
Udan
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
Mary E
ME
Dickinson
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; The Hospital For Sick Children, Toronto, Ontario, Canada.
R Mark
RM
Henkelman
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001158:Arteries / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins; D004622:Embryo, Mammalian; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018994:Myosin Light Chains / Q000172:deficiency / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics; D038081:Organogenesis / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C524495:Mlc2a protein, mouse; D018994:Myosin Light Chains