title: Intraflagellar transport/Hedgehog-related signaling components couple sensory cilium morphology and serotonin biosynthesis in Caenorhabditis elegans.
abstract: Intraflagellar transport in cilia has been proposed as a crucial mediator of Hedgehog signal transduction during embryonic pattern formation in both vertebrates and invertebrates. Here, we show that the Hh receptor Patched-related factor DAF-6 and intraflagellar transport modulate serotonin production in Caenorhabditis elegans animals, by remodeling the architecture of dendritic cilia of a pair of ADF serotonergic chemosensory neurons. Wild-type animals under aversive environment drastically reduce DAF-6 expression in glia-like cells surrounding the cilia of chemosensory neurons, resulting in cilium structural remodeling and upregulation of the serotonin-biosynthesis enzyme tryptophan hydroxylase tph-1 in the ADF neurons. These cellular and molecular modifications are reversed when the environment improves. Mutants of daf-6 or intraflagellar transport constitutively upregulate tph-1 expression. Epistasis analyses indicate that DAF-6/intraflagellar transport and the OCR-2/OSM-9 TRPV channel act in concert, regulating two layers of activation of tph-1 in the ADF neurons. The TRPV signaling turns on tph-1 expression under favorable and aversive conditions, whereas inactivation of DAF-6 by stress results in further upregulation of tph-1 independently of OCR-2/OSM-9 activity. Behavioral analyses suggest that serotonin facilitates larval animals resuming development when the environment improves. Our study revealed the cilium structure of serotonergic neurons as a trigger of regulated serotonin production, and demonstrated that a Hedgehog-related signaling component is dynamically regulated by environment and underscores neuroplasticity of serotonergic neurons in C. elegans under stress and stress recovery.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Moussaif
authors.forename: Ji Ying
authors.initials: JY
authors.lastname: Sze