Two tcf3 genes cooperate to pattern the zebrafish brain.
Caudalizing factors operate in the context of Wnt/beta-catenin signaling to induce gene expression in discrete compartments along the rostral-caudal axis of the developing vertebrate nervous system. In zebrafish, basal repression of caudal genes is achieved through the function of Headless (Hdl), a Tcf3 homolog. In this study, we show that a second Tcf3 homolog, Tcf3b, limits caudalization caused by loss of Hdl function and although this Lef/Tcf family member can rescue hdl mutants, Lef1 cannot. Wnts can antagonize repression mediated by Tcf3 and this derepression is dependent on a Tcf3 beta-catenin binding domain. Systematic changes in gene expression caused by reduced Tcf3 function help predict the shape of a caudalizing activity gradient that defines compartments along the rostral-caudal axis. In addition, Tcf3b has a second and unique role in the morphogenesis of rhombomere boundaries, indicating that it controls multiple aspects of brain development.
Dorsky
Richard I
RI
Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA. richard.dorsky@hsc.utah.edu
Itoh
Motoyuki
M
Moon
Randall T
RT
Chitnis
Ajay
A
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology*; D003598:Cytoskeletal Proteins; D024002:HMGB Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000378:metabolism; D016372:RNA, Antisense; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins
D003598:Cytoskeletal Proteins; D024002:HMGB Proteins; D011506:Proteins; D016372:RNA, Antisense; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C544914:tcf7l1a protein, zebrafish; C544915:tcf7l1b protein, zebrafish; C094521:wnt8a protein, zebrafish