RT Journal Article
SR Electronic
T1 Novel transient cell clusters provide a possible link between early neural activity and angiogenesis in the neonatal mouse retina
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.04.502860
DO 10.1101/2022.08.04.502860
A1 Jean de Montigny
A1 Courtney Thorne
A1 Diya Bhattacharya
A1 Dimitrios Bousoulas Sertedakis
A1 Vidhyasankar Krishnamoorthy
A1 Fernando Rozenblit
A1 Tim Gollisch
A1 Evelyne Sernagor
YR 2022
UL http://biorxiv.org/content/early/2022/08/06/2022.08.04.502860.abstract
AB Developing neurons become spontaneously active while growing blood vessels begin to irrigate their surroundings. However, surprising little is known about early interactions between neural activity and angiogenesis. In the neonatal mouse retina, spontaneous waves of impulses sweep across the ganglion cell layer (GCL), just underneath the growing superficial vascular plexus. We discovered clusters of transient auto-fluorescent cells in the GCL, forming an annulus that co-localizes with the frontline of the growing plexus. Blood vessel density is highest within cluster areas, suggesting their involvement in angiogenesis. Once the clusters and blood vessels reach the retinal periphery by the end of the first postnatal week, the clusters disappear, eliminated by microglial phagocytosis. Electrical imaging suggests that they have their own electrophysiological signature. Blocking Pannexin1 (PANX1) hemi-channels with probenecid blocks the waves and the fluorescent clusters disappear following prolonged exposure to the drug. Spontaneous waves’ initiation points follow a developmental center-to-periphery progression similar to the cluster cells. We suggest that these transient cells are specialized, hyperactive neurons residing in the GCL. They generate spontaneous activity hotspots, thereby triggering waves through purinergic paracrine signaling via PANX1 hemi-channels. The strong activity generated around these hotspots triggers angiogenesis, attracting new blood vessels that provide local oxygen supply. Signaling through PANX-1 attracts microglia that establish contact with these cells, eventually leading to their elimination by phagocytosis. These cluster cells may provide the first evidence that specialized transient neuronal populations guide angiogenesis in the developing CNS through neural activity.Competing Interest StatementThe authors have declared no competing interest.