Abstract
In the ascidian Ciona intestinalis larval development and metamorphosis require a complex interplay of events, including nitric oxide (NO) production, MAP kinases (ERK, JNK) and caspase-3 activation. We have previously shown that NO levels affect the rate of metamorphosis, regulate caspase activity and promote an oxidative stress pathway, resulting in protein nitration. Here, we report that NO down-regulates MAP kinase phosphatases (mkps) expression affecting positively ERK signaling. By pharmacological approach, we observed that the reduction of endogenous NO levels caused a decrease of ERK phosphorylation, whereas increasing levels of NO induced ERK activation. We have also identified the ERK gene network affected by NO, including mpk1, mpk3 and some key developmental genes by quantitative gene expression analysis. We demonstrate that NO induces an ERK-independent down-regulation of mkp1 and mkp3, responsible for maintaining the ERK phosphorylation levels necessary for transcription of key metamorphic genes, such as the hormone receptor rev-erb and the van willebrand protein vwa1c. These results add new insights into the role played by NO during larval development and metamorphosis in Ciona, highlighting the cross-talk between different signaling pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Ciona intestinalis / drug effects
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Ciona intestinalis / genetics*
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Ciona intestinalis / growth & development
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Ciona intestinalis / metabolism
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Profiling
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Gene Expression Regulation, Developmental*
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Larva / drug effects
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Larva / genetics
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Larva / growth & development
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Larva / metabolism
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MAP Kinase Kinase 4 / genetics
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MAP Kinase Kinase 4 / metabolism
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Metamorphosis, Biological / genetics*
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Mitogen-Activated Protein Kinase Phosphatases / antagonists & inhibitors
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Mitogen-Activated Protein Kinase Phosphatases / genetics*
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Mitogen-Activated Protein Kinase Phosphatases / metabolism
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Molecular Sequence Data
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Nitric Oxide / metabolism*
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Nitric Oxide / pharmacology
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Phosphorylation
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Sequence Alignment
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Signal Transduction / drug effects*
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Signal Transduction / genetics
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von Willebrand Factor / genetics
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von Willebrand Factor / metabolism
Substances
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Receptors, Cytoplasmic and Nuclear
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von Willebrand Factor
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Nitric Oxide
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Extracellular Signal-Regulated MAP Kinases
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Phosphatases
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Caspase 3
Grants and funding
This work was supported by institutional funds. E. E. has been supported by a SZN PhD fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.