title: Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and require tfap2a for expression of the neurotransmitter phenotype.
abstract: Tfap2a is a transcriptional activator expressed in many different cell types, including neurons, neural crest derivatives and epidermis. We show that mutations at the zebrafish locus previously called mont blanc (mob) or lockjaw (low) encode tfap2a. The mutant phenotype reveals that tfap2a is essential for the development of hindbrain noradrenergic (NA) neurons of the locus coeruleus, medulla and area postrema, as well as for sympathetic NA neurons, epibranchial placode derived visceral sensory ganglia, and craniofacial and trunk crest derivatives. We focus our analysis on the role of tfap2a NA differentiation in the CNS. In the locus coeruleus, Phox2a and Tfap2a are co-expressed and are both required for NA development. By contrast, in the medulla Phox2a and Tfap2a are expressed in adjacent overlapping domains, but only tfap2a activity is required for NA differentiation, as NA neurons develop normally in soulless/phox2a mutant medulla. phox2a and tfap2a do not appear to affect each others expression. Our studies show that two distinct inductive mechanisms control NA development in the zebrafish hindbrain. For the posterior hindbrain, we identify retinoic acid as an important signal to induce NA differentiation in the medulla oblongata and area postrema, where it expands the tfap2a expression domain and thus acts upstream of tfap2a. By contrast, previous work revealed Fgf8 to be involved in specification of NA neurons in the locus coeruleus. Thus, although the inductive signals may be distinct, hindbrain NA neurons of the locus coeruleus and the posterior groups both require Tfap2a to establish their noradrenergic identity.
authors.affiliation: Developmental Biology, Institute Biology 1, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Holzschuh
authors.forename: Alejandro
authors.initials: A
authors.lastname: Barrallo-Gimeno
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Ettl
authors.forename: Katrin
authors.initials: K
authors.lastname: Durr
authors.forename: Ela W
authors.initials: EW
authors.lastname: Knapik
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Driever
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004627:Embryonic Induction; D005260:Female; D005728:Ganglia, Sympathetic / Q000002:abnormalities / Q000166:cytology / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D010641:Phenotype; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D015027:Zebrafish / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins
chemical_list: D000316:Adrenergic alpha-Agonists; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D029961:Zebrafish Proteins; C493676:tfap2a protein, zebrafish; D012701:Serotonin; D014212:Tretinoin; D009638:Norepinephrine