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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
A role for Syndecan-4 in neural induction involving ERK- and PKC-dependent pathways
1Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Abstract:
Syndecan-4 (Syn4) is a heparan sulphate proteoglycan that is able to bind to some growth factors, including FGF, and can control cell migration. Here we describe a new role for Syn4 in neural induction in Xenopus. Syn4 is expressed in dorsal ectoderm and becomes restricted to the neural plate. Knockdown with antisense morpholino oligonucleotides reveals that Syn4 is required for the expression of neural markers in the neural plate and in neuralised animal caps. Injection of Syn4 mRNA induces the cell-autonomous expression of neural, but not mesodermal, markers. We show that two parallel pathways are involved in the neuralising activity of Syn4: FGF/ERK, which is sensitive to dominant-negative FGF receptor and to the inhibitors SU5402 and U0126, and a PKC pathway, which is dependent on the intracellular domain of Syn4. Neural induction by Syn4 through the PKC pathway requires inhibition of PKCdelta and activation of PKCalpha. We show that PKCalpha inhibits Rac GTPase and that c-Jun is a target of Rac. These findings might account for previous reports implicating PKC in neural induction and allow us to propose a link between FGF and PKC signalling pathways during neural induction.
Insights
Syndecan-4 (Syn4) plays a crucial role in neural induction in Xenopus embryos. This heparan sulfate proteoglycan activates both FGF/ERK and PKC signaling pathways to promote neural cell development.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Neuroscience
Background:
- Syndecan-4 (Syn4) is a heparan sulfate proteoglycan known to regulate cell migration and bind growth factors like FGF.
- Its precise role in early embryonic development, particularly neural induction, remains largely unexplored.
Purpose of the Study:
- To investigate the novel function of Syndecan-4 (Syn4) in the process of neural induction in Xenopus embryos.
- To elucidate the molecular mechanisms and signaling pathways by which Syn4 mediates neural development.
Main Methods:
- Utilized antisense morpholino oligonucleotides for Syn4 knockdown in Xenopus embryos.
- Performed Syn4 mRNA injection to assess cell-autonomous effects on neural marker expression.
- Investigated signaling pathways using dominant-negative FGF receptor, specific inhibitors (SU5402, U0126), and manipulation of PKC isoforms (PKCdelta, PKCalpha).
Main Results:
- Syn4 knockdown inhibited neural marker expression in the neural plate and animal caps.
- Syn4 overexpression induced cell-autonomous neural marker expression.
- Syn4's neuralizing activity involves parallel FGF/ERK and PKC signaling pathways.
- The PKC pathway activation requires inhibition of PKCdelta and activation of PKCalpha, which in turn affects Rac GTPase and c-Jun.
Conclusions:
- Syndecan-4 is essential for neural induction in Xenopus.
- Syn4 acts through both FGF/ERK and a novel PKC-dependent pathway involving PKCalpha, Rac GTPase, and c-Jun.
- These findings establish a link between FGF and PKC signaling in neural induction.
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