FoxF is essential for FGF-induced migration of heart progenitor cells in the ascidian Ciona intestinalis.
Heart development requires precise coordination of morphogenetic movements with progressive cell fate specification and differentiation. In ascidian embryos, FGF/MAPK-mediated activation of the transcription factor Ets1/2 is required for heart tissue specification and cell migration. We found that FoxF is one of the first genes to be activated in heart precursors in response to FGF signaling. We identified the FoxF minimal heart enhancer and used a cis-trans complementation test to show that Ets1/2 can interact with the FoxF enhancer in vivo. Next, we found that FoxF function is required downstream and in parallel to the FGF/MAPK/Ets cascade for cell migration. In addition, we demonstrated that targeted expression of a dominant-negative form of FoxF inhibits cell migration but not heart differentiation, resulting in a striking phenotype: a beating heart at an ectopic location within the body cavity of juveniles. Taken together, our results indicate that FoxF is a direct target of FGF signaling and is predominantly involved in the regulation of heart cell migration.
Beh
Jeni
J
Center for Integrative Genomics, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
Shi
Weiyang
W
Levine
Mike
M
Davidson
Brad
B
Christiaen
Lionel
L
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D002938:Ciona intestinalis / Q000166:cytology / Q000196:embryology* / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005346:Fibroblast Growth Factors / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006339:Heart Rate / Q000235:genetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*
D051858:Forkhead Transcription Factors; D005346:Fibroblast Growth Factors; D020929:Mitogen-Activated Protein Kinase Kinases