Mechanism of MASH1 induction by ASK1 and ATRA in adult neural progenitors

Muna Elmi, Romanus Faigle, Weiwen Yang, Yoshiki Matsumoto, Erica Rosenqvist, Keiko Funa

Research output: Contribution to journalArticle

Abstract

The molecular mechanisms underlying differentiation and lineage commitment in neural stem cells are just beginning to be understood, however the molecules involved in this process and their functions remain largely unknown. Here we studied the effects and downstream signals of apoptosis signal-regulating kinase 1 (ASK1) together with all-trans retinoic acid (ATRA) on neuronal differentiation in adult hippocampus-derived progenitor (AHP) cells. Following ASK1 over-expression and ATRA treatment in AHPs, a larger number of cells differentiated into neurons and the MASH1 promoter became activated. Analyzing downstream effector molecules of ASK1 or ATRA targeting the MASH1 promoter revealed that the myocyte enhancer factor 2C (MEF2C) mediated ASK1 signalling, while activation of Sp1 was involved in ATRA signalling. Chromatin immunoprecipitation assay on the promoter revealed that ASK1 induced binding of MEF2C and Ca 2+/calmodulin-dependent kinase II to the MASH1 promoter. Taken together, ASK1 and ATRA activate MEF2C and Sp1, respectively, and up-regulate MASH1 protein expression.

Original languageEnglish (US)
Pages (from-to)248-259
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume36
Issue number2
DOIs
StatePublished - Oct 2007
Externally publishedYes

Fingerprint

MAP Kinase Kinase Kinase 5
Tretinoin
MEF2 Transcription Factors
Calcium-Calmodulin-Dependent Protein Kinases
Neural Stem Cells
Chromatin Immunoprecipitation
Hippocampus
Up-Regulation
Stem Cells
Cell Count
Neurons

Keywords

  • ASK1
  • ATRA
  • Chromatin
  • MASH1
  • MEF2C

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Mechanism of MASH1 induction by ASK1 and ATRA in adult neural progenitors. / Elmi, Muna; Faigle, Romanus; Yang, Weiwen; Matsumoto, Yoshiki; Rosenqvist, Erica; Funa, Keiko.

In: Molecular and Cellular Neuroscience, Vol. 36, No. 2, 10.2007, p. 248-259.

Research output: Contribution to journalArticle

Elmi, Muna ; Faigle, Romanus ; Yang, Weiwen ; Matsumoto, Yoshiki ; Rosenqvist, Erica ; Funa, Keiko. / Mechanism of MASH1 induction by ASK1 and ATRA in adult neural progenitors. In: Molecular and Cellular Neuroscience. 2007 ; Vol. 36, No. 2. pp. 248-259.
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