title: Locus coeruleus neurons originate in alar rhombomere 1 and migrate into the basal plate: Studies in chick and mouse embryos.
abstract: We investigated in the mouse and chick the neuroepithelial origin and development of the locus coeruleus (LoC), the most important noradrenergic neuronal population in the brain. We first studied the topography of the developing LoC in the hindbrain, using as markers the key noradrenergic marker gene Dbh and the transcription factors Phox2a and Phox2b (upstream of Dbh). In both mouse and chicken, LoC neurons first appear arranged linearly along the middle one-third of the alar plate of rhombomere 1 (r1), collinear to a reference ventricular longitudinal band that early on expresses Phox2a and Phox2b in the alar plate of r2 and later expands to r1. Double-labeling experiments with LoC markers (Dbh or Phox2a) and either alar (Pax7 and Rnx3) or basal (Otp) genetic markers suggested that LoC cells migrate from their origin in the alar plate to a final position in the lateral basal plate. To corroborate these suggestions experimentally and determine the precise origin of the LoC, we fate mapped the LoC in the chick at stage HH11 by using quail-chick homotopic grafts. The experimental results confirmed that the LoC originates in the alar plate throughout the rostrocaudal extent of r1 and ruled out a rostrocaudal translocation. They also corroborated a ventralward tangential migration of LoC cells into the lateral basal plate, where the postmigratory LoC primordium is located. Comparisons with neighboring alar r1-derived cell populations established that LoC neurons originate outside the cerebellum, in a matrix area intercalated dorsoventrally between the sources of the prospective vestibular and trigeminal columns.
authors.affiliation: Department of Human Anatomy and Psychobiology, Medical School, University of Murcia, Spain. pilaroca@um.es
authors.forename: Pilar
authors.initials: P
authors.lastname: Aroca
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lorente-Cánovas
authors.forename: Francisco R
authors.initials: FR
authors.lastname: Mateos
authors.forename: Luis
authors.initials: L
authors.lastname: Puelles
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement; D002642:Chick Embryo; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D047108:Embryonic Development; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000166:cytology* / Q000196:embryology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051763:PAX7 Transcription Factor / Q000378:metabolism; D011784:Quail; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism / Q000637:transplantation; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; C109220:NBPhox protein; D009419:Nerve Tissue Proteins; C088624:Otp protein, mouse; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; C491060:Phox2a protein, mouse; D014157:Transcription Factors; D004299:Dopamine beta-Hydroxylase