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 D Camenisch, Margaret Buckingham, Anne M. Moon

Research output: Contribution to journalArticle

92 Citations (Scopus)

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 TGFβ 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.

Original languageEnglish (US)
Pages (from-to)3599-3610
Number of pages12
JournalDevelopment
Volume135
Issue number21
DOIs
StatePublished - 2008

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Mesoderm
Morphogenesis
Neural Crest
Endothelial Cells
Extracellular Matrix
Myocardium

Keywords

  • Autocrine signaling
  • Epithelial-mesenchymal transformation
  • FGF
  • Heart development
  • Mouse
  • Outflow tract
  • Second heart field

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Park, E. J., Watanabe, Y., Smyth, G., Miyagawa-Tomita, S., Meyers, E., Klingensmith, J., ... Moon, A. M. (2008). An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart. Development, 135(21), 3599-3610. https://doi.org/10.1242/dev.025437

An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart. / Park, Eon Joo; Watanabe, Yusuke; Smyth, Graham; Miyagawa-Tomita, Sachiko; Meyers, Erik; Klingensmith, John; Camenisch, Todd D; Buckingham, Margaret; Moon, Anne M.

In: Development, Vol. 135, No. 21, 2008, p. 3599-3610.

Research output: Contribution to journalArticle

Park, EJ, Watanabe, Y, Smyth, G, Miyagawa-Tomita, S, Meyers, E, Klingensmith, J, Camenisch, TD, Buckingham, M & Moon, AM 2008, 'An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart', Development, vol. 135, no. 21, pp. 3599-3610. https://doi.org/10.1242/dev.025437
Park, Eon Joo ; Watanabe, Yusuke ; Smyth, Graham ; Miyagawa-Tomita, Sachiko ; Meyers, Erik ; Klingensmith, John ; Camenisch, Todd D ; Buckingham, Margaret ; Moon, Anne M. / An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart. In: Development. 2008 ; Vol. 135, No. 21. pp. 3599-3610.
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