title: Bmp5/7 in concert with the mid-hindbrain organizer control development of noradrenergic locus coeruleus neurons.
abstract: The locus coeruleus (LC) which is the major noradrenergic nucleus in the brain develops under the influence of Bmps secreted by the roof plate and Fgf8 emitted from the mid-hindbrain organizer. We studied the development of the LC in different Bmp mouse mutants and report the absence of this nucleus in Bmp5(-/-);Bmp7(-/-) double knockouts. Notably, genes marking organizers and neuronal populations adjacent to the LC precursor field are unperturbed in Bmp5(-/-);Bmp7(-/-) animals. In addition, we found that in En1(+/Otx2) mutants in which the caudal Otx2 expression domain and thereby the mid-hindbrain organizer are shifted caudally, LC neurons are concomitantly reduced along with Bmp5/7. Complementing these results, Otx1(-/-);Otx2(+/-) mutants, in which the mid-hinbrain organizer is shifted rostrally, show a rostrally extended Bmp5 expression area and an increase in LC neurons. Taken together, our data indicate that LC development requires either Bmp5 or Bmp7, and one is able to compensate for the loss of the other. In addition, we conclude that the position of the mid-hindbrain organizer determines the size of the LC and propose that Bmp5/7 play an important role in mediating this organizer function.
authors.affiliation: Zlotowski Center for Neuroscience, Department of Morphology, Division of Basic Sciences, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er Sheva, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Tilleman
authors.forename: Vicky
authors.initials: V
authors.lastname: Hakim
authors.forename: Orna
authors.initials: O
authors.lastname: Novikov
authors.forename: Keren
authors.initials: K
authors.lastname: Liser
authors.forename: Limor
authors.initials: L
authors.lastname: Nashelsky
authors.forename: Michela
authors.initials: M
authors.lastname: Di Salvio
authors.forename: Mark
authors.initials: M
authors.lastname: Krauthammer
authors.forename: Oren
authors.initials: O
authors.lastname: Scheffner
authors.forename: Ido
authors.initials: I
authors.lastname: Maor
authors.forename: Oded
authors.initials: O
authors.lastname: Mayseless
authors.forename: Inbal
authors.initials: I
authors.lastname: Meir
authors.forename: Galya
authors.initials: G
authors.lastname: Kayam
authors.forename: Dalit
authors.initials: D
authors.lastname: Sela-Donenfeld
authors.forename: Antonio
authors.initials: A
authors.lastname: Simeone
authors.forename: Claude
authors.initials: C
authors.lastname: Brodski
mesh_terms: D000818:Animals; D017209:Apoptosis; D055417:Bone Morphogenetic Protein 5 / Q000378:metabolism*; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008125:Locus Coeruleus / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D055417:Bone Morphogenetic Protein 5; D055419:Bone Morphogenetic Protein 7; C496457:Fgf8 protein, mouse; D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; C497656:Otx1 protein, mouse; C497660:Otx2 protein, mouse; C491060:Phox2a protein, mouse; D051524:Fibroblast Growth Factor 8; D009638:Norepinephrine