Some parameters, such as dam crest width and initiation water level, may not influence the peak outflow rate and breach size of a single dam obviously, but may influence the cascading breaching of several dams significantly through the amplification effect.
Changes in these pathways may collectively result in the unique neural crest and outflow tract phenotypes observed in ILK mutants.
Our results demonstrate that ILK plays essential roles in neural crest and outflow tract development by mediating complex crosstalk between cell matrix and multiple signaling pathways.
Notch intercellular signalling has been implicated in multiple aspects of heart development including cushion development, trabecular growth, atrioventricular patterning, neural crest differentiation, and outflow tract development.
Of the BMP signaling receptors, BMP receptor type1A (BMPR1alsolso known as ALK3) is required in endothelial cells for normal development of the cardiac cushions [ Kaneko et al., 2008; Song et al., 2007], in myocardial cells for normal trabeculae and endocardial cushion formation [ Gaussin et al., 2005], and in neural crest for normal outflow tract septation [ Stottmann et al., 2004].
Indeed, ectodermic deletion of the Bmp receptor gene Bmpr1a caused cleft lip [25], and conditional ablation of the same gene in neural crest cells caused cardiac outflow tract defects [26].
We did not observe increased apoptosis over the different time points between E10.5 and E12.5, and correspondingly neural crest contribution to the outflow tract was not significantly reduced at E11.5 (see Supplementary material online, Figure S3B D ).
We used magnetic resonance and confocal microscopy to determine that the volume of myocardium in the looped heart was dramatically reduced and the compact layer of myocardium was thinner after neural crest ablation, especially in the outflow tract and ventricular regions.
In contrast, neural crest cell contribution to the outflow tract cushions was normal in Robo1 mutants.
