title: Histone deacetylase 1 is required to repress Notch target gene expression during zebrafish neurogenesis and to maintain the production of motoneurones in response to hedgehog signalling.
abstract: Histone deacetylases (Hdacs) are widely implicated as key components of transcriptional silencing mechanisms. Here, I show that hdac1 is specifically required in the zebrafish embryonic CNS to maintain neurogenesis. In hdac1 mutant embryos, the Notch-responsive E(spl)-related neurogenic gene her6 is ectopically expressed at distinct sites within the developing CNS and proneural gene expression is correspondingly reduced or eliminated. Using an hdac1-specific morpholino, I show that this requirement for hdac1 is epistatic to the requirement for Notch signalling. Consequently, hdac1-deficient embryos exhibit several defects of neuronal specification and patterning, including a dramatic deficit of hedgehog-dependent branchiomotor neurones that is refractory to elevated levels of hedgehog signalling. Thus, in the zebrafish embryo, hdac1 is an essential component of the transcriptional silencing machinery that supports the formation and subsequent differentiation of neuronal precursors.
authors.affiliation: Centre for Developmental Genetics, School of Medicine and Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK. v.t.cunliffe@shef.ac.uk
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Cunliffe
mesh_terms: D000818:Animals; D002455:Cell Division; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053823:Hedgehog Proteins; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics*; D009024:Morphogenesis / Q000235:genetics*; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009420:Nervous System / Q000196:embryology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051880:Receptors, Notch; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D051880:Receptors, Notch; D015534:Trans-Activators; D029961:Zebrafish Proteins; C488363:HDAC1 protein, zebrafish; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases