Neurofibromatosis-1 Regulates Neuronal and Glial Cell Differentiation from Neuroglial Progenitors In Vivo by Both cAMP- and Ras-Dependent Mechanisms

B. Hegedűs, Biplab Dasgupta, Jung Eun Shin, Ryan J. Emnett, Elizabeth K. Hart-Mahon, Lynda Elghazi, Ernesto Bernal-Mizrachi, David H. Gutmann

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Individuals with neurofibromatosis type 1 (NF1) develop abnormalities of both neuronal and glial cell lineages, suggesting that the NF1 protein neurofibromin is an essential regulator of neuroglial progenitor function. In this regard, Nf1-deficient embryonic telencephalic neurospheres exhibit increased self-renewal and prolonged survival as explants in vivo. Using a newly developed brain lipid binding protein (BLBP)-Cre mouse strain to study the role of neurofibromin in neural progenitor cell function in the intact animal, we now show that neuroglial progenitor Nf1 inactivation results in increased glial lineage proliferation and abnormal neuronal differentiation in vivo. Whereas the glial cell lineage abnormalities are recapitulated by activated Ras or Akt expression in vivo, the neuronal abnormalities were Ras- and Akt independent and reflected impaired cAMP generation in Nf1-deficient cells in vivo and in vitro. Together, these findings demonstrate that neurofibromin is required for normal glial and neuronal development involving separable Ras-dependent and cAMP-dependent mechanisms.

Original languageEnglish
Pages (from-to)443-457
Number of pages15
JournalCell Stem Cell
Volume1
Issue number4
DOIs
Publication statusPublished - Oct 11 2007

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Neurofibromin 1
Neurofibromatosis 1
Neuroglia
Cell Differentiation
Cell Lineage
Telencephalon
Stem Cells

Keywords

  • MOLNEURO
  • STEMCELL

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Neurofibromatosis-1 Regulates Neuronal and Glial Cell Differentiation from Neuroglial Progenitors In Vivo by Both cAMP- and Ras-Dependent Mechanisms. / Hegedűs, B.; Dasgupta, Biplab; Shin, Jung Eun; Emnett, Ryan J.; Hart-Mahon, Elizabeth K.; Elghazi, Lynda; Bernal-Mizrachi, Ernesto; Gutmann, David H.

In: Cell Stem Cell, Vol. 1, No. 4, 11.10.2007, p. 443-457.

Research output: Contribution to journalArticle

Hegedűs, B. ; Dasgupta, Biplab ; Shin, Jung Eun ; Emnett, Ryan J. ; Hart-Mahon, Elizabeth K. ; Elghazi, Lynda ; Bernal-Mizrachi, Ernesto ; Gutmann, David H. / Neurofibromatosis-1 Regulates Neuronal and Glial Cell Differentiation from Neuroglial Progenitors In Vivo by Both cAMP- and Ras-Dependent Mechanisms. In: Cell Stem Cell. 2007 ; Vol. 1, No. 4. pp. 443-457.
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