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Regulation of Nodal signaling propagation by receptor interactions and positive feedback

Hannes Preiß1, Anna C Kögler1,2, David Mörsdorf1

  • 1Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany.

Elife
|September 23, 2022
PubMed

Insights

Activin receptors (Acvr) mediate Nodal signaling during vertebrate development. This study identifies specific Acvr Type I and Type II receptors in zebrafish, revealing their roles in germ layer patterning and Nodal distribution.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Nodal signals pattern germ layers during vertebrate embryogenesis.
  • The classical model involves Nodal binding to Activin receptors (Acvr) and Tdgf1.
  • The specific Acvr paralogs mediating Nodal signaling and their impact on Nodal distribution remain unclear.

Purpose of the Study:

  • To characterize zebrafish Acvr Type I and Type II homologs.
  • To determine the roles of Acvr paralogs in Nodal signaling and germ layer patterning.
  • To investigate the influence of receptor binding on Nodal distribution.

Main Methods:

  • Transcript characterization of Acvr Type I and Type II homologs.
  • Generation of zebrafish mutants and use of morpholino knockdown.
  • CRISPR F0 knockout (KO) for compound loss-of-function analysis.
  • Quantitative analyses and expression manipulations.

Main Results:

  • Most Acvr receptor transcripts are maternally deposited and present during zebrafish embryogenesis.
  • Acvr2 homologs exhibit partial redundancy and independence from Nodal in early patterning.
  • Acvr1b-a and Acvr1b-b act redundantly as major mediators of Nodal signaling.
  • Feedback-regulated receptors and co-receptors directly influence Nodal diffusion and distribution.

Conclusions:

  • Specific Acvr Type I and Type II receptors play crucial, partly redundant roles in zebrafish germ layer patterning.
  • Receptor-ligand interactions regulate Nodal distribution, providing a mechanism for spatial restriction of Nodal signaling.
Keywords:
DiffusionGerm layer patterningGradient formationNodal signalingReceptorsdevelopmental biologyzebrafish

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