Foxn4 directly regulates tbx2b expression and atrioventricular canal formation.
Cardiac chamber formation represents an essential evolutionary milestone that allows for the heart to receive (atrium) and pump (ventricle) blood throughout a closed circulatory system. Here, we reveal a novel transcriptional pathway between foxn4 and tbx genes that facilitates this evolutionary event. We show that the zebrafish gene slipjig, which encodes Foxn4, regulates the formation of the atrioventricular (AV) canal to divide the heart. sli/foxn4 is expressed in the AV canal, and its encoded product binds to a highly conserved tbx2 enhancer domain that contains Foxn4- and T-box-binding sites, both necessary to regulate tbx2b expression in the AV canal.
Chi
Neil C
NC
Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, University of California, San Francisco, San Francisco, California 94158, USA.
Shaw
Robin M
RM
De Val
Sarah
S
Kang
Guson
G
Jan
Lily Y
LY
Black
Brian L
BL
Stainier
Didier Y R
DY
D000818:Animals; D030801:Animals, Genetically Modified; D001283:Atrioventricular Node / Q000196:embryology*; D001665:Binding Sites; D002874:Chromosome Mapping; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006325:Heart Atria / Q000196:embryology* / Q000378:metabolism; D006352:Heart Ventricles / Q000196:embryology* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
D017931:DNA Primers; D051858:Forkhead Transcription Factors; C528811:Foxn4 protein, zebrafish; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D029961:Zebrafish Proteins; C120107:tbx2b protein, zebrafish