Npr3 regulates neural crest and cranial placode progenitors formation through its dual function as clearance and signaling receptor

Abstract

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.

Data availability

All data generated and analyzed in this study are included in the manuscript and supporting files. Source date files have been provided for all Figures.

Article and author information

Author details

  1. Arun Devotta

    Department of Molecular Pathobiology, New York University, New York, United States
    Competing interests
    Arun Devotta, is affiliated with Regeneron Pharmaceuticals. The author has no financial interests to declare..
  2. Hugo Juraver-Geslin

    Department of Molecular Pathobiology, New York University, New York, United States
    Competing interests
    No competing interests declared.
  3. Casey Griffin

    Department of Molecular Pathobiology, New York University, New York, United States
    Competing interests
    No competing interests declared.
  4. Jean-Pierre Saint-Jeannet

    Department of Molecular Pathobiology, New York University, New York, United States
    For correspondence
    jsj4@nyu.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3259-2103

Funding

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.

Reviewing Editor

  1. Carole LaBonne, Northwestern University, United States

Ethics

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.

Version history

  1. Received: October 7, 2022
  2. Preprint posted: October 22, 2022 (view preprint)
  3. Accepted: May 9, 2023
  4. Accepted Manuscript published: May 10, 2023 (version 1)
  5. Version of Record published: May 25, 2023 (version 2)

Copyright

© 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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  1. Arun Devotta
  2. Hugo Juraver-Geslin
  3. Casey Griffin
  4. Jean-Pierre Saint-Jeannet
(2023)
Npr3 regulates neural crest and cranial placode progenitors formation through its dual function as clearance and signaling receptor
eLife 12:e84036.
https://doi.org/10.7554/eLife.84036

Share this article

https://doi.org/10.7554/eLife.84036

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