Transition between quiescence and activation of stem/progenitor cells in response to physiological conditions plays an important role in maintenance of tissue homeostasis, and its failure is closely associated with tumor formation and aging. Quiescent stem/progenitor cells in newly hatched C. eleganslarvae become activated to initiate postembryonic development when ample food is supplied. We have previously reported that the insulin/IGF signaling pathway and its downstream effector, miR-235 in the hypodermis regulate this quiescence in multiple types of somatic progenitor cells (1,2). However, the intercellular signaling mechanism by which the hypodermis controls these undifferentiated cells still remains to be delineated. We found that one of miR-235 targets, a hedgehog related gene,
grl-7, can activate quiescent neural progenitors when overexpressed even under the starvation condition. Loss of
ptr-18, which encodes evolutionally conserved PTR (also called PTCHD), results in inappropriate activation of quiescent neural progenitors in starved L1 larvae after hatch. This phenotype is suppressed by inhibition of
grl-7. During late embryogenesis, both PTR-18 and GRL-7 reporter proteins are first detected around the apical side of hypodermal cells. The GRL-7 reporter is observed outside the PTR-18, suggesting that GRL-7 is secreted. Around hatching, these reporter proteins subsequently disappear from it and colocalize on endosomes and lysosomes in a
rab-5 dependent manner. Furthermore, efficient internalization of the GRL-7 reporter requiresactivity of
ptr-18. These findings together suggest that
ptr-18 prevents precocious activation of neural progenitor cells by temporally restricting activity of GRL-7through endocytosis. 1. Kasuga et al., Nature 2013 2. Fukuyama et al., Current Biology 2015