Neuronal migration and cAMP: the primary cilium beats the tempo!

In this article published in Science Advances1, the Plasticity and Development of Neural Networks team2(UMR8246) collaborating with the Dynamics of Intracellular Signaling and Therapeutic Targets team3 (UMR8256) reveal an entirely new mechanism regulating neuronal migration. Using biosensor imaging on mouse brain slices, they show that the primary cilium regulates migration by periodic production of cAMP activating Protein Kinase A at the centrosome. This regulates the rhythm of saltatory migration through nucleus/centrosome coupling. These results thus highlight a cAMPc/PKA link between the primary cilium and the centrosome, essential for migrating neurons and which could exist in other types of ciliated cells.

This article was the subject of a news item on the INSB website, and on the CNRS Délégation Paris-Centre website.

© Isabelle Caillé

Figure: A: Immunohistochemical labeling of a young migrating GFP positive neuron (green) revealing a positive Arl13B primary cilium (gray) linked to the positive gamma-Tubulin centrosome (red). Scale bar: 10 µm. B1: migrating neuron transfected with a cAMP biosensor. A cAMP-rich zone appears in red (arrows) at times 3 and 6 minutes during nuclear translocation. B2: diagram corresponding to the different stages of migration of the neuron filmed in B1. A cAMP hotspot (red dot) is visible at the centrosome of the neuron during nuclear translocation (times 3 and 6 minutes) and absent during pauses (times 1 and 8 minutes). N: nucleus, CTR: centrosome. C: schematic representation of the primary cilium and the centrosome of a migrating neuron. During nuclear translocation, the Adenylate Cyclase 3 of the primary cilium produces cAMP (red) which activates the Protein Kinase A at the centrosome and thus regulates the rhythm of migration.

© Isabelle Caillé

Migrating neuron transfected with a cAMP biosensor: a cAMP hotspot is present at the centrosome during nuclear translocation.