Article

An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart.

Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
Development (impact factor: 6.6). 12/2008; 135(21):3599-610. DOI:10.1242/dev.025437 pp.3599-610
Source: PubMed

ABSTRACT In order to understand how secreted signals regulate complex morphogenetic events, it is crucial to identify their cellular targets. By conditional inactivation of Fgfr1 and Fgfr2 and overexpression of the FGF antagonist sprouty 2 in different cell types, we have dissected the role of FGF signaling during heart outflow tract development in mouse. Contrary to expectation, cardiac neural crest and endothelial cells are not primary paracrine targets. FGF signaling within second heart field mesoderm is required for remodeling of the outflow tract: when disrupted, outflow myocardium fails to produce extracellular matrix and TGFbeta and BMP signals essential for endothelial cell transformation and invasion of cardiac neural crest. We conclude that an autocrine regulatory loop, initiated by the reception of FGF signals by the mesoderm, regulates correct morphogenesis at the arterial pole of the heart. These findings provide new insight into how FGF signaling regulates context-dependent cellular responses during development.

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Keywords

autocrine regulatory loop
 
BMP signals essential
 
cardiac neural
 
cellular targets
 
complex morphogenetic events
 
different cell types
 
endothelial cell transformation
 
endothelial cells
 
extracellular matrix
 
FGF antagonist sprouty 2
 
FGF signaling regulates context-dependent cellular responses
 
Fgfr1
 
Fgfr2
 
heart outflow tract development
 
new insight
 
outflow myocardium
 
outflow tract
 
overexpression
 
regulates correct morphogenesis
 
second heart field mesoderm