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

Hadas Tilleman; Vicky Hakim; Orna Novikov; Keren Liser; Limor Nashelsky; Michela Di Salvio; Mark Krauthammer; Oren Scheffner; Ido Maor; Oded Mayseless; Inbal Meir; Galya Kayam; Dalit Sela-Donenfeld; Antonio Simeone; Claude Brodski

doi:10.1016/j.mcn.2010.05.003

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

Hadas Tilleman, Vicky Hakim, Orna Novikov, Keren Liser, Limor Nashelsky, Michela Di Salvio, Mark Krauthammer, Oren Scheffner, Ido Maor, Oded Mayseless, Inbal Meir, Galya Kayam, Dalit Sela-Donenfeld, Antonio Simeone, Claude Brodski^*

^*Corresponding author for this work

The Koret School of Veterinary Medicine

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English
Pages (from-to)	1-11
Number of pages	11
Journal	Molecular and Cellular Neuroscience
Volume	45
Issue number	1
DOIs	https://doi.org/10.1016/j.mcn.2010.05.003
State	Published - Sep 2010

Bibliographical note

Funding Information:
We are grateful to Elizabeth J. Robertson (University of Oxford, UK) for her generous gift of Bmp6 −/− and Bmp7 −/− mutant mice and to Jean-François Brunet (École Normale Supérieure, Paris, France) for his generous gift of Phox2a antisera. This work was supported by research grants from the Israel Science Foundation grant No. 864/05 , the National Institute for Psychobiology in Israel — founded by the Charles E. Smith Family ( 7-2004-05 , 212-2007-08 ), and by the Israeli Ministry of Health , Chief Scientist's Office ( 3-00000-3546 ) to C. B.; the Italian Association for Cancer Research (AIRC) and the “Stem Cell Project” of Fondazione Roma to A.S.; the Israel Science Foundation grant 161/07 to D.S-D.

Keywords

Bmp5
Bmp7
Bone morphogenetic proteins
Development
Hindbrain
Isthmic organizer
Locus coeruleus
Mid-hindbrain organizer
Noradrenaline
Otx2

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10.1016/j.mcn.2010.05.003

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Tilleman, H., Hakim, V., Novikov, O., Liser, K., Nashelsky, L., Di Salvio, M., Krauthammer, M., Scheffner, O., Maor, I., Mayseless, O., Meir, I., Kayam, G., Sela-Donenfeld, D., Simeone, A., & Brodski, C. (2010). Bmp5/7 in concert with the mid-hindbrain organizer control development of noradrenergic locus coeruleus neurons. Molecular and Cellular Neuroscience, 45(1), 1-11. https://doi.org/10.1016/j.mcn.2010.05.003

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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.",

keywords = "Bmp5, Bmp7, Bone morphogenetic proteins, Development, Hindbrain, Isthmic organizer, Locus coeruleus, Mid-hindbrain organizer, Noradrenaline, Otx2",

author = "Hadas Tilleman and Vicky Hakim and Orna Novikov and Keren Liser and Limor Nashelsky and {Di Salvio}, Michela and Mark Krauthammer and Oren Scheffner and Ido Maor and Oded Mayseless and Inbal Meir and Galya Kayam and Dalit Sela-Donenfeld and Antonio Simeone and Claude Brodski",

note = "Funding Information: We are grateful to Elizabeth J. Robertson (University of Oxford, UK) for her generous gift of Bmp6 −/− and Bmp7 −/− mutant mice and to Jean-Fran{\c c}ois Brunet ({\'E}cole Normale Sup{\'e}rieure, Paris, France) for his generous gift of Phox2a antisera. This work was supported by research grants from the Israel Science Foundation grant No. 864/05 , the National Institute for Psychobiology in Israel — founded by the Charles E. Smith Family ( 7-2004-05 , 212-2007-08 ), and by the Israeli Ministry of Health , Chief Scientist's Office ( 3-00000-3546 ) to C. B.; the Italian Association for Cancer Research (AIRC) and the “Stem Cell Project” of Fondazione Roma to A.S.; the Israel Science Foundation grant 161/07 to D.S-D.",

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Tilleman, H, Hakim, V, Novikov, O, Liser, K, Nashelsky, L, Di Salvio, M, Krauthammer, M, Scheffner, O, Maor, I, Mayseless, O, Meir, I, Kayam, G, Sela-Donenfeld, D, Simeone, A & Brodski, C 2010, 'Bmp5/7 in concert with the mid-hindbrain organizer control development of noradrenergic locus coeruleus neurons', Molecular and Cellular Neuroscience, vol. 45, no. 1, pp. 1-11. https://doi.org/10.1016/j.mcn.2010.05.003

TY - JOUR

T1 - Bmp5/7 in concert with the mid-hindbrain organizer control development of noradrenergic locus coeruleus neurons

AU - Tilleman, Hadas

AU - Hakim, Vicky

AU - Novikov, Orna

AU - Liser, Keren

AU - Nashelsky, Limor

AU - Di Salvio, Michela

AU - Krauthammer, Mark

AU - Scheffner, Oren

AU - Maor, Ido

AU - Mayseless, Oded

AU - Meir, Inbal

AU - Kayam, Galya

AU - Sela-Donenfeld, Dalit

AU - Simeone, Antonio

AU - Brodski, Claude

N1 - Funding Information: We are grateful to Elizabeth J. Robertson (University of Oxford, UK) for her generous gift of Bmp6 −/− and Bmp7 −/− mutant mice and to Jean-François Brunet (École Normale Supérieure, Paris, France) for his generous gift of Phox2a antisera. This work was supported by research grants from the Israel Science Foundation grant No. 864/05 , the National Institute for Psychobiology in Israel — founded by the Charles E. Smith Family ( 7-2004-05 , 212-2007-08 ), and by the Israeli Ministry of Health , Chief Scientist's Office ( 3-00000-3546 ) to C. B.; the Italian Association for Cancer Research (AIRC) and the “Stem Cell Project” of Fondazione Roma to A.S.; the Israel Science Foundation grant 161/07 to D.S-D.

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

KW - Bmp5

KW - Bmp7

KW - Bone morphogenetic proteins

KW - Development

KW - Hindbrain

KW - Isthmic organizer

KW - Locus coeruleus

KW - Mid-hindbrain organizer

KW - Noradrenaline

KW - Otx2

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ER -

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

Abstract

Bibliographical note

Keywords

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