Team Teases Out Germline Integrity, Protection Pathway During Worm Developmental Pause

McGill University researchers reporting in PLOS Genetics dig into a neuronal pathway that appears to help protect the germline from excess proliferation or damage during a developmental arrest diapause state dubbed dauer in the worm model organism Caenorhabditis elegans. Following from prior studies that found an AMP-kinase role in successful quiescence during, and recovery from, dauer, the team turned to forward genetic screening to find eight mutant alleles that appeared to dial down germ cell defects or sterility after dauer in AMPK-mutant worms. That set included a mutant form of TBC-7, a gene coding for an apparent RAB-7-regulatory protein with suspected RabGAP pathway functions in neuronal cells that is typically phosphorylated by AMPK and further regulated by a pair of microRNAs controlled by the kinase. "By first modulating the activity of TBC-7, AMPK enhances RAB-7 activation, while later in the diapause, AMPK promotes the activity of two microRNAs that impinge on the tbc-7 transcript, thereby blocking its expression," the authors propose. "This results in a cell non-autonomous pro-quiescent signal that instructs the germ cells to modify their chromatin landscape and associated gene expression, ensuring that the germ cells remain reproductively competent for the duration of the diapause stage."