title: HoxB8 in noradrenergic specification and differentiation of the autonomic nervous system.
abstract: Different prespecification of mesencephalic and trunk neural crest cells determines their response to environmental differentiation signals and contributes to the generation of different autonomic neuron subtypes, parasympathetic ciliary neurons in the head and trunk noradrenergic sympathetic neurons. The differentiation of ciliary and sympathetic neurons shares many features, including the initial BMP-induced expression of noradrenergic characteristics that is, however, subsequently lost in ciliary but maintained in sympathetic neurons. The molecular basis of specific prespecification and differentiation patterns has remained unclear. We show here that HoxB gene expression in trunk neural crest is maintained in sympathetic neurons. Ectopic expression of a single HoxB gene, HoxB8, in mesencephalic neural crest results in a strongly increased expression of sympathetic neuron characteristics like the transcription factor Hand2, tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) in ciliary neurons. Other subtype-specific properties like RGS4 and RCad are not induced. HoxB8 has only minor effects in postmitotic ciliary neurons and is unable to induce TH and DBH in the enteric nervous system. Thus, we conclude that HoxB8 acts by maintaining noradrenergic properties transiently expressed in ciliary neuron progenitors during normal development. HoxC8, HoxB9, HoxB1 and HoxD10 elicit either small and transient or no effects on noradrenergic differentiation, suggesting a selective effect of HoxB8. These results implicate that Hox genes contribute to the differential development of autonomic neuron precursors by maintaining noradrenergic properties in the trunk sympathetic neuron lineage.
authors.affiliation: Research Group Developmental Neurobiology, Max Planck Institute for Brain Research, Frankfurt/Main, Germany.
authors.forename: Leslie
authors.initials: L
authors.lastname: Huber
authors.forename: Marius
authors.initials: M
authors.lastname: Ferdin
authors.forename: Julia
authors.initials: J
authors.lastname: Holzmann
authors.forename: Jutta
authors.initials: J
authors.lastname: Stubbusch
authors.forename: Hermann
authors.initials: H
authors.lastname: Rohrer
mesh_terms: D059331:Adrenergic Neurons / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001341:Autonomic Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002642:Chick Embryo; D002645:Chickens; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D054259:Neural Tube / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D018398:Homeodomain Proteins; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase