Bmp5/7 in concert with the mid-hindbrain organizer control development of noradrenergic locus coeruleus neurons

被引:18
|
作者
Tilleman, Hadas [1 ]
Hakim, Vicky [1 ]
Novikov, Orna [1 ]
Liser, Keren [1 ]
Nashelsky, Limor [1 ]
Di Salvio, Michela [2 ]
Krauthammer, Mark [1 ]
Scheffner, Oren [1 ]
Maor, Ido [1 ]
Mayseless, Oded [1 ]
Meir, Inbal [1 ]
Kayam, Galya [3 ]
Sela-Donenfeld, Dalit [3 ]
Simeone, Antonio [2 ,4 ]
Brodski, Claude [1 ]
机构
[1] Ben Gurion Univ Negev, Fac Hlth Sci, Div Basic Sci, Zlotowski Ctr Neurosci,Dept Morphol, Beer Sheva, Israel
[2] CEINGE Biotecnol Avanzate, I-80145 Naples, Italy
[3] Hebrew Univ Jerusalem, Koret Sch Vet Med, Robert H Smith Fac Agr Food & Environm, Rehovot, Israel
[4] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80131 Naples, Italy
基金
以色列科学基金会;
关键词
Locus coeruleus; Development; Mid-hindbrain organizer; Isthmic organizer; Bone morphogenetic proteins; Bmp5; Bmp7; Otx2; Noradrenaline; Hindbrain; BONE MORPHOGENETIC PROTEINS; CELL-SURVIVAL; IN-VIVO; EXPRESSION; FGF8; SPECIFICATION; MIDBRAIN; PLATE; OTX2; DIFFERENTIATION;
D O I
10.1016/j.mcn.2010.05.003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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(-/-); 8mp7(-/-) 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. (C) 2010 Elsevier Inc. All rights reserved.
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页码:1 / 11
页数:11
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