Npr3 regulates neural crest and cranial placode progenitors formation through its dual function as clearance and signaling receptor
Natriuretic peptide signaling has been implicated in a broad range of physiological processes, regulating blood volume and pressure, ventricular hypertrophy, fat metabolism, and long bone growth. Here we describe a completely novel role for natriuretic peptide signaling in the control of neural crest (NC) and cranial placode (CP) progenitors formation. Among the components of this signaling pathway, we show that natriuretic peptide receptor 3 (Npr3) plays a pivotal role by differentially regulating two developmental programs through its dual function as clearance and signaling receptor. Using a combination of MO-based knockdowns, pharmacological inhibitors and rescue assays we demonstrate that Npr3 cooperate with guanylate cyclase natriuretic peptide receptor 1 (Npr1) and natriuretic peptides (Nppa/Nppc) to regulate NC and CP formation, pointing at a broad requirement of this signaling pathway in early embryogenesis. We propose that Npr3 acts as a clearance receptor to regulate local concentrations of natriuretic peptides for optimal cGMP production through Npr1 activation, and as a signaling receptor to control cAMP levels through inhibition of adenylyl cyclase. The intracellular modulation of these second messengers therefore participates in the segregation of NC and CP cell populations.
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Article and author information
National Institutes of Health (DE025806)
- Jean-Pierre Saint-Jeannet
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: The work was performed in accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and was approved by the Institutional Animal Care and Use Committee of New York University, protocol #IA16-00052.
- Carole LaBonne, Northwestern University, United States
- Received: October 7, 2022
- Preprint posted: October 22, 2022 (view preprint)
- Accepted: May 9, 2023
- Accepted Manuscript published: May 10, 2023 (version 1)
- Version of Record published: May 25, 2023 (version 2)
© 2023, Devotta et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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