Extracellular signal-regulated kinase (ERK) 5 is necessary and sufficient to specify cortical neuronal fate

Lidong Liu, Paige Cundiff, Glen Abel, Yupeng Wang, Roland Faigle, Hiroyuki Sakagami, Mei Xu, Zhengui Xia

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Multipotent cortical progenitor cells differentiate into neurons and glial cells during development; however, mechanisms governing the specification of progenitors to a neuronal fate are not well understood. Although both extrinsic and intrinsic factors regulate this process, little is known about kinase signaling mechanisms that direct neuronal fate. Here, we report that extracellular signal-regulated kinase (ERK) 5 is expressed and active in proliferating cortical progenitors. Lentiviral gene delivery of a dominant negative ERK5 or dominant negative MAP kinase kinase 5 reduced the number of neurons generated from rat cortical progenitor cells in culture, whereas constitutive activation of ERK5 increased the production of neurons. Furthermore, when cortical progenitor cells were treated with ciliary neurotrophic factor, which induces precocious glial differentiation, ERK5 activation still promoted neuronal fate while suppressing glial differentiation. Our data also indicate that ERK5 does not directly regulate proliferation or apoptosis of cultured cortical progenitors. We conclude that ERK5 is necessary and sufficient to stimulate the generation of neurons from cortical progenitors. These results suggest a previously uncharacterized function for ERK5 signaling during brain development and raise the interesting possibility that extrinsic factors may instruct cortical progenitors to become neurons by activating the ERK5 pathway.

Original languageEnglish (US)
Pages (from-to)9697-9702
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - Jun 20 2006
Externally publishedYes


  • Neural progenitor cell
  • Neural stem cell
  • Neurogenesis

ASJC Scopus subject areas

  • General


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