First published online October 10, 2008
Development 135, 2101e (2008)
© The Company of Biologists Limited
An outflow of cardiac FGF signalling
Nearly 1% of newborn babies have heart defects, often caused by abnormal
cardiac outflow tract (OFT) development. The OFT is initially a myocardial
tube that forms from a mesodermal cell population called the second heart
field (SHF). During OFT remodelling, the myocardial cells secrete
extracellular matrix (ECM) to form the OFT cushions, which are invaded by
neural crest cells and by endothelial cells that line the OFT myocardium. The
endothelial cells undergo an endothelial-to-mesenchymal transition (EMT) and,
finally, the OFT septates into the aorta and the pulmonary artery and
realigns/rotates into its final position. Two papers in this issue of
Development provide new information about how FGF signalling controls
these complex morphogenetic events in mice. On
p. 3599, Anne Moon
and colleagues report that an FGF signal produced in the SHF mesoderm
establishes an autocrine loop that regulates OFT development in vivo. The
researchers inactivate two FGF receptors (Fgfr1 and Fgfr2)
and overexpress the FGF antagonist sprouty 2 in various embryonic cell types
to dissect FGF's role during OFT development. Unexpectedly, given the paradigm
of FGF paracrine signalling established in other tissues, the neural crest
cells and endothelial cells are not the direct targets of the SHF-derived FGF.
Instead, interrupting FGF signalling in SHF mesodermal cells prevents the
secretion of signalling and ECM factors by their progeny, which secondarily
perturbs endothelial and neural crest cell invasion into the OFT cushions, and
also the EMT and OFT septation. On
p. 3611, Fen Wang and
colleagues use ablation of Frs2
, which encodes an adaptor
protein that links FGF receptor kinases to multiple signalling pathways, to
investigate the downstream pathways that mediate FGF signalling in cardiac
progenitors. They report that ablation of Frs2 in SHF
mesodermal cells affects their expansion into the OFT myocardium and results
in OFT misalignment and hypoplasia. In addition, EMT and neural crest
recruitment into the OFT cushions are defective in Frs2
mutants, resulting in OFT septation defects. Taken together, the results of
these two papers provide new molecular insights into the regulation of OFT
morphogenesis by FGF signalling.
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Related articles in Development:
- An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart
- Eon Joo Park, Yusuke Watanabe, Graham Smyth, Sachiko Miyagawa-Tomita, Erik Meyers, John Klingensmith, Todd Camenisch, Margaret Buckingham, and Anne M. Moon
Development 2008 135: 3599-3610.
[Abstract]
[Full Text]
- Frs2-deficiency in cardiac progenitors disrupts a subset of FGF signals required for outflow tract morphogenesis
- Jue Zhang, Yongshun Lin, Yongyou Zhang, Yongsheng Lan, Chunhong Lin, Anne M. Moon, Robert J. Schwartz, James F. Martin, and Fen Wang
Development 2008 135: 3611-3622.
[Abstract]
[Full Text]
