PT  - JOURNAL ARTICLE
AU  - Sean Corcoran
AU  - Anjeli Mase
AU  - Yousuf Hashmi
AU  - Debra Ouyang
AU  - Jordan Augsburger
AU  - Thea Jacobs
AU  - Katelyn Kukar
AU  - Katja Brückner
TI  - Regulation of blood cell transdifferentiation by oxygen sensing neurons in <em>Drosophila</em>
AID  - 10.1101/2020.04.22.056622
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.22.056622
4099  - http://biorxiv.org/content/early/2020/04/23/2020.04.22.056622.short
4100  - http://biorxiv.org/content/early/2020/04/23/2020.04.22.056622.full
AB  - Transdifferentiation of functionally specialized cell types, which omits the need for stem or progenitor cells, is known across the animal kingdom. However, in the blood cell system it remains largely unclear how transdifferentiation is regulated in vivo. Here we reveal the environmental control of blood cell transdifferentiation in a Drosophila melanogaster model. Functional lineage tracing provides new in vivo evidence for direct 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. Evidence for this stems from specific neuron ablation, and transient silencing or activation of these neurons by Kir2.1 or TrpA1, respectively. Crystal cells develop from plasmatocytes in 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 governing blood cell transdifferentiation in vivo, suggesting similar principles in vertebrate systems where environmental sensors and blood cell populations coincide.HighlightsFunctional lineage tracing confirms in vivo transdifferentiation in a Drosophila model of hematopoiesisBlood cell transdifferentiation is promoted by active sensory neurons of the caudal sensory cones of the Drosophila larvaSensory cone neurons detect oxygen through atypical guanylyl cyclases and promote blood cell transdifferentiationCompeting Interest StatementThe authors have declared no competing interest.