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Cited by 254

The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.

Required, tissue-specific roles for Fgf8 in outflow tract formation and remodeling

Open access
Park, Eon Joo, Ogden, Lisa A., Talbot, Amy, Evans, Sylvia, Cai, Chen-Leng, Black, Brian L., Frank, Deborah U., Moon, Anne M.·2006·Development
DOI 10.1242/dev.02367
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Abstract

Fibroblast growth factor 8 (Fgf8) is a secreted signaling protein expressed in numerous temporospatial domains that are potentially relevant to cardiovascular development. However, the pathogenesis of complex cardiac and outflow tract defects observed in Fgf8-deficient mice, and the specific source(s) of Fgf8 required for outflow tract formation and subsequent remodeling are unknown. A detailed examination of the timing and location of Fgf8 production revealed previously unappreciated expression in a subset of primary heart field cells; Fgf8 is also expressed throughout the anterior heart field (AHF) mesoderm and in pharyngeal endoderm at the crescent and early somite stages. We used conditional mutagenesis to examine the requirements for Fgf8 function in these different expression domains during heart and outflow tract morphogenesis. Formation of the primary heart tube and the addition of right ventricular and outflow tract myocardium depend on autocrine Fgf8 signaling in cardiac crescent mesoderm. Loss of Fgf8 in this domain resulted in decreased expression of the Fgf8 target gene Erm,and aberrant production of Isl1 and its target Mef2c in the anterior heart field, thus linking Fgf8 signaling with transcription factor networks that regulate survival and proliferation of the anterior heart field. We further found that mesodermal- and endodermal-derived Fgf8 perform specific functions during outflow tract remodeling: mesodermal Fgf8 is required for correct alignment of the outflow tract and ventricles, whereas activity of Fgf8 emanating from pharyngeal endoderm regulates outflow tract septation. These findings provide a novel insight into how the formation and remodeling of primary and anterior heart field-derived structures rely on Fgf8 signals from discrete temporospatial domains.

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Metadata

Authors
Park, E. J., Ogden, L. A., Talbot, A., Evans, S., Cai, C.-L., Black, B. L., Frank, D. U., & Moon, A. M.
Venue
Development
Publisher
The Company of Biologists
Published
2006-06-15
Volume
133
Issue
12
Pages
2419-2433
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.02367
OpenAlex
W2050184933
Cited by
254
References
70
FWCI
7.74
Type
journal article
Language
en
Open access
bronze

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