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Grafting of Beads into Developing Chicken Embryo Limbs to Identify Signal Transduction Pathways Affecting Gene Expression
Published on: January 17, 2016
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.
Abstract:
The MAPK/ERK pathway regulates a variety of physiological cellular functions, including cell proliferation and survival. It is abnormally activated in many types of human cancers in response to driver mutations in regulators of this pathway that trigger tumor initiation. The early steps of oncogenic progression downstream of ERK overactivation are poorly understood due to a lack of appropriate models. We show here that ERK1/2 overactivation in the trunk neural tube of the chicken embryo through expression of a constitutively active form of the upstream kinase MEK1 (MEK1ca), rapidly provokes a profound change in the transcriptional signature of developing spinal cord cells. These changes are concordant with a previously established role of the tyrosine kinase receptor ligand FGF8 acting via the ERK1/2 effectors to maintain an undifferentiated state. Furthermore, we show that MEK1ca-transfected spinal cord cells lose neuronal identity, retain caudal markers, and ectopically express potential effector oncogenes, such as AQP1. MEK1ca expression in the developing spinal cord from the chicken embryo is thus a tractable in vivo model to identify the mechanisms fostering neoplasia and malignancy in ERK-induced tumorigenesis of neural origins.
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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