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A balance of BMP and notch activity regulates neurogenesis and olfactory nerve formation.

Maier E, Nord H, von Hofsten J, Gunhaga L - PLoS ONE (2011)

Bottom Line: Here, we provide evidence that both modulated Notch and bone morphogenetic protein (BMP) signaling affect the generation of neurons in the olfactory epithelium and reduce the number of migratory neurons, so called epithelioid cells.These data provide new insights into the early generation of neurons in the olfactory epithelium and the initial formation of the olfactory nerve tract.Our results present a novel mechanism in which BMP signals negatively affect Notch activity in a dominant manner in the olfactory epithelium, thereby regulating neurogenesis and explain why a balance of BMP and Notch activity is critical for the generation of neurons and proper development of the olfactory nerve.

View Article: PubMed Central - PubMed

Affiliation: Umeå Center for Molecular Medicine, Umeå University, Umeå, Sweden.

ABSTRACT
Although the function of the adult olfactory system has been thoroughly studied, the molecular mechanisms regulating the initial formation of the olfactory nerve, the first cranial nerve, remain poorly defined. Here, we provide evidence that both modulated Notch and bone morphogenetic protein (BMP) signaling affect the generation of neurons in the olfactory epithelium and reduce the number of migratory neurons, so called epithelioid cells. We show that this reduction of epithelial and migratory neurons is followed by a subsequent failure or complete absence of olfactory nerve formation. These data provide new insights into the early generation of neurons in the olfactory epithelium and the initial formation of the olfactory nerve tract. Our results present a novel mechanism in which BMP signals negatively affect Notch activity in a dominant manner in the olfactory epithelium, thereby regulating neurogenesis and explain why a balance of BMP and Notch activity is critical for the generation of neurons and proper development of the olfactory nerve.

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The generation of migratory neurons is regulated by Notch and BMP signaling.(A) The total number of migratory neurons was unaffected by electroporation of GFP, but was significantly decreased (* = p<0,05 by t-test) in the Alk6-, Noggin- and caNotch1-electroporated olfactory pit compared to the non-electroporated side. Electroporation of dnMAMLI resulted in a non-significant decrease of migratory neurons compared to the non-electroporated side. (B) Immunohistochemical images of the generation of HuC/D+ migratory neurons in electroporated embryos. Both gain-and-loss of BMP and Notch function reduced the number of migratory HuC/D+ neurons. (C) Graphs indicate the percentages of HuC/D+ neurons (red) and HuC/D+/GFP+ neurons (yellow) in the olfactory epithelium and in the migratory mass. Error bars in A and C indicate s.e.m.
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pone-0017379-g003: The generation of migratory neurons is regulated by Notch and BMP signaling.(A) The total number of migratory neurons was unaffected by electroporation of GFP, but was significantly decreased (* = p<0,05 by t-test) in the Alk6-, Noggin- and caNotch1-electroporated olfactory pit compared to the non-electroporated side. Electroporation of dnMAMLI resulted in a non-significant decrease of migratory neurons compared to the non-electroporated side. (B) Immunohistochemical images of the generation of HuC/D+ migratory neurons in electroporated embryos. Both gain-and-loss of BMP and Notch function reduced the number of migratory HuC/D+ neurons. (C) Graphs indicate the percentages of HuC/D+ neurons (red) and HuC/D+/GFP+ neurons (yellow) in the olfactory epithelium and in the migratory mass. Error bars in A and C indicate s.e.m.

Mentions: BMP activity has previously been shown to play an important role in the early specification and patterning of the olfactory placode [2], [8], and for the differentiation of neurons in the olfactory sensory epithelium [8], [9], [10]. To examine in more detail how BMP signals affect the development of migratory neurons from the olfactory epithelium in intact embryos, we electroporated GFP alone or together with Alk6 or Noggin in stage 12/13 chick embryos in the olfactory placodal region, and cultured the embryos in ovo to approximately stage 19. Embryos with GFP expression in the olfactory pit region were selected for further analyses, and differentiated neurons were detected by HuC/D antibody staining. To evaluate whether BMP activity affects the generation of migratory neurons, we quantified the total number of migratory neurons in the electroporated embryos. In Alk6-transfected embryos (n = 7), where BMP signaling was elevated, the total number of migratory neurons was significantly decreased compared to the non-electroporated control side (Fig. 3A,B). Also in Noggin-electroporated embryos (n = 7), the total number of migratory neurons was significantly decreased compared to the non-electroporated control side (Fig. 3A,B). Thus, both gain and loss of BMP activity reduce the number of migratory neurons, indicating that the generation of migratory neurons is dependent on BMP levels in the olfactory epithelium.


A balance of BMP and notch activity regulates neurogenesis and olfactory nerve formation.

Maier E, Nord H, von Hofsten J, Gunhaga L - PLoS ONE (2011)

The generation of migratory neurons is regulated by Notch and BMP signaling.(A) The total number of migratory neurons was unaffected by electroporation of GFP, but was significantly decreased (* = p<0,05 by t-test) in the Alk6-, Noggin- and caNotch1-electroporated olfactory pit compared to the non-electroporated side. Electroporation of dnMAMLI resulted in a non-significant decrease of migratory neurons compared to the non-electroporated side. (B) Immunohistochemical images of the generation of HuC/D+ migratory neurons in electroporated embryos. Both gain-and-loss of BMP and Notch function reduced the number of migratory HuC/D+ neurons. (C) Graphs indicate the percentages of HuC/D+ neurons (red) and HuC/D+/GFP+ neurons (yellow) in the olfactory epithelium and in the migratory mass. Error bars in A and C indicate s.e.m.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3044177&req=5

pone-0017379-g003: The generation of migratory neurons is regulated by Notch and BMP signaling.(A) The total number of migratory neurons was unaffected by electroporation of GFP, but was significantly decreased (* = p<0,05 by t-test) in the Alk6-, Noggin- and caNotch1-electroporated olfactory pit compared to the non-electroporated side. Electroporation of dnMAMLI resulted in a non-significant decrease of migratory neurons compared to the non-electroporated side. (B) Immunohistochemical images of the generation of HuC/D+ migratory neurons in electroporated embryos. Both gain-and-loss of BMP and Notch function reduced the number of migratory HuC/D+ neurons. (C) Graphs indicate the percentages of HuC/D+ neurons (red) and HuC/D+/GFP+ neurons (yellow) in the olfactory epithelium and in the migratory mass. Error bars in A and C indicate s.e.m.
Mentions: BMP activity has previously been shown to play an important role in the early specification and patterning of the olfactory placode [2], [8], and for the differentiation of neurons in the olfactory sensory epithelium [8], [9], [10]. To examine in more detail how BMP signals affect the development of migratory neurons from the olfactory epithelium in intact embryos, we electroporated GFP alone or together with Alk6 or Noggin in stage 12/13 chick embryos in the olfactory placodal region, and cultured the embryos in ovo to approximately stage 19. Embryos with GFP expression in the olfactory pit region were selected for further analyses, and differentiated neurons were detected by HuC/D antibody staining. To evaluate whether BMP activity affects the generation of migratory neurons, we quantified the total number of migratory neurons in the electroporated embryos. In Alk6-transfected embryos (n = 7), where BMP signaling was elevated, the total number of migratory neurons was significantly decreased compared to the non-electroporated control side (Fig. 3A,B). Also in Noggin-electroporated embryos (n = 7), the total number of migratory neurons was significantly decreased compared to the non-electroporated control side (Fig. 3A,B). Thus, both gain and loss of BMP activity reduce the number of migratory neurons, indicating that the generation of migratory neurons is dependent on BMP levels in the olfactory epithelium.

Bottom Line: Here, we provide evidence that both modulated Notch and bone morphogenetic protein (BMP) signaling affect the generation of neurons in the olfactory epithelium and reduce the number of migratory neurons, so called epithelioid cells.These data provide new insights into the early generation of neurons in the olfactory epithelium and the initial formation of the olfactory nerve tract.Our results present a novel mechanism in which BMP signals negatively affect Notch activity in a dominant manner in the olfactory epithelium, thereby regulating neurogenesis and explain why a balance of BMP and Notch activity is critical for the generation of neurons and proper development of the olfactory nerve.

View Article: PubMed Central - PubMed

Affiliation: Umeå Center for Molecular Medicine, Umeå University, Umeå, Sweden.

ABSTRACT
Although the function of the adult olfactory system has been thoroughly studied, the molecular mechanisms regulating the initial formation of the olfactory nerve, the first cranial nerve, remain poorly defined. Here, we provide evidence that both modulated Notch and bone morphogenetic protein (BMP) signaling affect the generation of neurons in the olfactory epithelium and reduce the number of migratory neurons, so called epithelioid cells. We show that this reduction of epithelial and migratory neurons is followed by a subsequent failure or complete absence of olfactory nerve formation. These data provide new insights into the early generation of neurons in the olfactory epithelium and the initial formation of the olfactory nerve tract. Our results present a novel mechanism in which BMP signals negatively affect Notch activity in a dominant manner in the olfactory epithelium, thereby regulating neurogenesis and explain why a balance of BMP and Notch activity is critical for the generation of neurons and proper development of the olfactory nerve.

Show MeSH
Related in: MedlinePlus