Elsevier

Developmental Biology

Volume 455, Issue 2, 15 November 2019, Pages 362-368
Developmental Biology

Role of JNK, MEK and adenylyl cyclase signalling in speed and directionality of enteric neural crest-derived cells

https://doi.org/10.1016/j.ydbio.2019.07.007Get rights and content
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Highlights

  • Changes to intracellular signalling pathways can alter ENCC migratory speed and/or direction.

  • Inhibition of JNK signalling decreased speed but did not affect directionality.

  • Activation of PKA or adenylyl cyclase decreased speed and increased caudal directionality of ENCC.

  • ENCC migratory speed and directionality can be uncoupled.

Abstract

Background

Cells derived from the neural crest colonize the developing gut and give rise to the enteric nervous system. The rate at which the ENCC population advances along the bowel will be affected by both the speed and directionality of individual ENCCs. The aim of the study was to use time-lapse imaging and pharmacological activators and inhibitors to examine the role of several intracellular signalling pathways in both the speed and the directionality of individual enteric neural crest-derived cells in intact explants of E12.5 mouse gut. Drugs that activate or inhibit intracellular components proposed to be involved in GDNF-RET and EDN3-ETB signalling in ENCCs were used.

Findings

Pharmacological inhibition of JNK significantly reduced ENCC speed but did not affect ENCC directionality. MEK inhibition did not affect ENCC speed or directionality. Pharmacological activation of adenylyl cyclase or PKA (a downstream cAMP-dependent kinase) resulted in a significant decrease in ENCC speed and an increase in caudal directionality of ENCCs. In addition, adenylyl cyclase activation also resulted in reduced cell-cell contact between ENCCs, however this was not observed following PKA activation, suggesting that the effects of cAMP on adhesion are not mediated by PKA.

Conclusions

JNK is required for normal ENCC migration speed, but not directionality, while cAMP signalling appears to regulate ENCC migration speed, directionality and adhesion. Collectively, our data demonstrate that intracellular signalling pathways can differentially affect the speed and directionality of migrating ENCCs.

Keywords

Enteric neural crest-derived cells
Migration
Directionality

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