Summary
Transdifferentiation generates functionally specialized cell types independent of stem or progenitor cells. Despite the unique nature of the process, it remains poorly understood how transdifferentiation is regulated in vivo. Here we reveal a mechanism of environmental control of blood cell transdifferentiation in a Drosophila melanogaster model of hematopoiesis. Using functional lineage tracing, we find in vivo evidence for transdifferentiation from macrophage-like plasmatocytes to crystal cells that execute melanization. Interestingly, this transdifferentiation is promoted by neuronal activity of a specific subset of sensory neurons, in the sensory cones at the caudal end of the larva, as is evidenced through genetic ablation, and manipulation of neuronal activity by Kir2.1 and TrpA1. Crystal cells develop from plasmatocyte clusters surrounding the sensory cones. Strikingly, environmental conditions trigger this process: oxygen sensing, through atypical guanylyl cyclases (Gyc88E, Gyc89Da, Gyc89Db) that are specifically expressed in sensory cone neurons, drives plasmatocyte-to-crystal cell transdifferentiation, as hypoxia or Gyc silencing cause crystal cell reduction and loss of transdifferentiation. Our findings reveal an unexpected functional and molecular link of environment-monitoring sensory neurons that govern blood cell transdifferentiation in vivo, suggesting similar principles in vertebrate systems where environmental sensors and blood cell populations coincide.
Highlights
Functional lineage tracing reveals in vivo transdifferentiation in a Drosophila model of hematopoiesis
Active sensory neurons of the caudal sensory cones promote blood cell transdifferentiation in the Drosophila larva
Environmental oxygen sensing through atypical guanylyl cyclases in sensory cone neurons drives blood cell transdifferentiation
Competing Interest Statement
The authors have declared no competing interest.