FGF-2-induced imbalance in early embryonic heart cell proliferation: a potential cause of late cardiovascular anomalies. Teratology 2000 Oct;62(4):189-94
Date
09/19/2000Pubmed ID
10992260DOI
10.1002/1096-9926(200010)62:4<189::AID-TERA4>3.0.CO;2-7Scopus ID
2-s2.0-0033808998 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
BACKGROUND: This laboratory previously demonstrated that placement of fibroblast growth factor-2 (FGF-2)-soaked beads adjacent to the developing ventricle at stage 24 caused cardiovascular anomalies by embryonic day 15. We sought to characterize early cellular changes that may suggest mechanisms for the abnormalities observed at day 15. Because levels of both myocyte proliferation and immunohistochemically detectable endogenous FGF-2 begin to decline before stage 24 in untreated embryos, it was of interest to determine whether exogenous FGF-2 might maintain cardiac myocyte proliferation at or near peak levels.
METHODS: Chick embryos were incubated to stage 18 (2.8 days), at which time beads soaked in phosphate-buffered saline (PBS) or 100 microg/ml FGF-2 were placed adjacent to the developing ventricle and development was allowed to continue. After 3 days (stage 29), bromodeoxyuridine (BrdU) was applied to mark dividing cells, followed by double fluorescent assessments to detect relative numbers of dividing and nondividing cells.
RESULTS: Quantitative image analysis, using Metamorph software, showed that exogenous FGF-2 caused a 62% increase in the overall number of dividing cells (P < 0.01), concomitant with a 25% increase in total cell number (cell density: P < 0.05). Expressed in relative terms, these changes corresponded to a 25% increase in the proliferation labeling index: 30% of all cells were proliferating in FGF-treated hearts, in contrast with only 24% in control hearts.
CONCLUSIONS: Taken together, these data suggest that an FGF-induced imbalance in myocardial cell proliferation at early developmental stages of heart development causes cardiovascular anomalies during late embryogenesis.
Author List
Franciosi JP, Bolender DL, Lough J, Kolesari GLAuthor
John W. Lough PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Abnormalities, Drug-InducedAnimals
Bromodeoxyuridine
Cardiovascular Abnormalities
Cell Count
Cell Division
Chick Embryo
Fibroblast Growth Factor 2
Fluorescent Antibody Technique, Indirect
Heart
Myocardium