Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord models early events in

Axelle Wilmerding1, Lauranne Bouteille1, Nathalie Caruso1

  • 1Aix-Marseille Univ, CNRS, Developmental Biology Institute of Marseille (IBDM), IBDM-UMR 7288, Case 907, Parc Scientifique de Luminy, Marseille Cedex 09 13288, France.

Neoplasia (New York, N.Y.)
|December 27, 2021
PubMed

Insights

Overactivating the MAPK/ERK pathway in developing spinal cord cells rapidly alters their gene expression, leading to a loss of neuronal identity and potential oncogene activation. This provides a new model for studying neural cancers.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Research

Background:

  • The MAPK/ERK pathway is crucial for cell proliferation and survival.
  • Abnormal activation of this pathway drives many human cancers.
  • Early oncogenic events downstream of ERK are not well understood due to limited models.

Purpose of the Study:

  • To investigate the early molecular events following ERK overactivation in the developing neural tube.
  • To establish a tractable in vivo model for studying ERK-induced neural tumorigenesis.

Main Methods:

  • Utilized a chicken embryo model.
  • Expressed a constitutively active form of MEK1 (MEK1ca) in the trunk neural tube to overactivate ERK1/2.
  • Analyzed transcriptional changes and cellular identity markers.

Main Results:

  • ERK1/2 overactivation caused rapid, profound transcriptional changes in spinal cord cells.
  • Cells lost neuronal identity and retained caudal markers.
  • Ectopic expression of potential oncogenes, such as AQP1, was observed.

Conclusions:

  • MEK1ca expression in the chicken embryo spinal cord serves as a valuable in vivo model.
  • This model can elucidate mechanisms of neoplasia and malignancy in neural cancers driven by ERK.
  • Findings highlight the role of ERK signaling in maintaining cellular identity and preventing oncogenic transformation.

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