Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis.
Although the functional importance of the hypothalamus has been demonstrated throughout vertebrates, the mechanisms controlling neurogenesis in this forebrain structure are poorly understood. We report that canonical Wnt signaling acts through Lef1 to regulate neurogenesis in the zebrafish hypothalamus. We show that Lef1 is required for proneural and neuronal gene expression, and for neuronal differentiation in the posterior hypothalamus. Furthermore, we find that this process is dependent on Wnt8b, a ligand of the canonical pathway expressed in the posterior hypothalamus, and that both Wnt8b and Lef1 act to mediate beta-catenin-dependent transcription in this region. Finally, we show that Lef1 associates in vivo with the promoter of sox3, which depends on Lef1 for its expression and can rescue neurogenesis in the absence of Lef1. The conserved presence of this pathway in other vertebrates suggests a common mechanism for regulating hypothalamic neurogenesis.
Lee
Ji Eun
JE
Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84105, USA.
Wu
Shan-Fu
SF
Goering
Lisa M
LM
Dorsky
Richard I
RI
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000378:metabolism; D007031:Hypothalamus / Q000196:embryology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism* / Q000502:physiology; D015027:Zebrafish / Q000196:embryology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins