Her5 acts as a prepattern factor that blocks neurogenin1 and coe2 expression upstream of Notch to inhibit neurogenesis at the midbrain-hindbrain boundary.
Neurogenesis in both vertebrates and invertebrates is tightly controlled in time and space involving both positive and negative regulators. We report here that the bHLH factor Her5 acts as a prepattern gene to prevent neurogenesis in the anlage of the midbrain/hindbrain boundary in the zebrafish neural plate. This involves selective suppression of both neurogenin1 (ngn1) and coe2 mRNA expression in a process that is independent of Notch signalling, and where inhibition of either ngn1 or coe2 expression is sufficient to prevent neuronal differentiation across the midbrain-hindbrain boundary. A ngn1 transgene faithfully responds to Her5 and deletion analysis of the transgene identifies an E-box in a ngn1 upstream enhancer to be required for repression by Her5. Together our data demonstrate a role of Her5 as a prepattern factor in the spatial definition of proneural domains in the zebrafish neural plate, in a manner similar to its Drosophila homologue Hairy.
Geling
Andrea
A
Zebrafish Neurogenetics Junior Research Group, Institute of Virology, Technical University-Munich, Trogerstrasse 4b, D-81675 Munich, Germany.
Plessy
Charles
C
Rastegar
Sepand
S
Strähle
Uwe
U
Bally-Cuif
Laure
L
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004628:Embryonic Structures / Q000033:anatomy & histology / Q000502:physiology; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D009024:Morphogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051880:Receptors, Notch; D012249:Rhombencephalon / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology; D029961:Zebrafish Proteins / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; D029961:Zebrafish Proteins; C474186:Her5 protein, zebrafish; C491765:ebf2 protein, zebrafish