Sleep drive is coupled to tissue damage via shedding of Caenorhabditis elegans EGFR ligand SISS-1.

The benefits of sleep extend beyond the nervous system. Peripheral tissues impact sleep regulation, and increased sleep is observed in response to damaging conditions, even those that selectively affect non-neuronal cells. However, the 'sleep need' signal released by stressed tissues is not known.

The tyrosine kinase inhibitor Gefitinib reduces stress-induced sleep, but not likely via LET-23/EGFR inhibition.

The anticancer drug Gefitinib is a tyrosine kinase inhibitor with selectivity for the Epidermal Growth Factor Receptor (EGFR/ErbB1). As the EGF receptor LET-23 shares notable structural homology over its kinase domain with human EGFR, we wished to examine whether Gefitinib treatment can interfere with LET-23-dependent processes. We show that Gefitinib disrupts stress-induced sleep (SIS) but does not impact EGF overexpression-induced sleep nor vulva induction.

Cellular damage, including wounding, drives stress-induced sleep.

Across animal phyla, sleep is associated with increased cellular repair, suggesting that cellular damage may be a core component of sleep pressure. In support of this notion, sleep in the nematode can be triggered by damaging conditions, including noxious heat, high salt, and ultraviolet light exposure. It is not clear, however, whether this stress-induced sleep (SIS) is a direct consequence of cellular damage, or of a resulting energy deficit, or whether it is triggered simply by the sensation of noxious conditions.

NPR-1 Modulates Plasticity in C. elegans Stress-Induced Sleep.

Sleep is beneficial yet antagonistic to critical functions such as foraging and escape, and we aim to understand how these competing drives are functionally integrated. C. elegans, which lives in reduced oxygen environments, engages in developmentally timed sleep (DTS) during larval stage transitions and engages in stress-induced sleep (SIS) during recovery from damaging conditions.

Food-Dependent Plasticity in Stress-Induced Sleep Is Mediated by TOR-FOXA and TGF-β Signaling.

Behavioral plasticity allows for context-dependent prioritization of competing drives, such as sleep and foraging. Despite the identification of neuropeptides and hormones implicated in dual control of sleep drive and appetite, our understanding of the mechanism underlying the conserved sleep-suppressing effect of food deprivation is limited. provides an intriguing model for the dissection of sleep function and regulation as these nematodes engage a quiescence program following exposure to noxious conditions, a phenomenon known as stress-induced sleep (SIS).

Cellular stress induces a protective sleep-like state in C. elegans.

Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis.

FMRFamide-like FLP-13 neuropeptides promote quiescence following heat stress in Caenorhabditis elegans.

Among the most important decisions an animal makes is whether to engage in active movement and feeding behavior or to become quiescent. The molecular signaling mechanisms underlying this decision remain largely unknown. The nematode Caenorhabditis elegans displays sleep-like quiescence following exposures that result in cellular stress.

LIN-42/PERIOD controls cyclical and developmental progression of C. elegans molts.

Background: Biological timing mechanisms that integrate cyclical and successive processes are not well understood. C. elegans molting cycles involve rhythmic cellular and animal behaviors linked to the periodic reconstruction of cuticles.

Paired and LIM class homeodomain proteins coordinate differentiation of the C. elegans ALA neuron.

The ancient origin of sleep is evidenced by deeply conserved signaling pathways regulating sleep-like behavior, such as signaling through the Epidermal growth factor receptor (EGFR). In Caenorhabditis elegans, a sleep-like state can be induced at any time during development or adulthood through conditional expression of LIN-3/EGF. The behavioral response to EGF is mediated by EGFR activity within a single cell, the ALA neuron, and mutations that impair ALA differentiation are expected to confer EGF-resistance.

Epidermal growth factor signaling induces behavioral quiescence in Caenorhabditis elegans.

The epidermal growth factor receptor (EGFR)/ErbB receptor tyrosine kinases regulate several aspects of development, including the development of the mammalian nervous system. ErbB signaling also has physiological effects on neuronal function, with influences on synaptic plasticity and daily cycles of activity. However, little is known about the effectors of EGFR activation in neurons.

Half pint regulates alternative splice site selection in Drosophila.

Alternative splicing is used by metazoans to increase protein diversity and to alter gene expression during development. However, few factors that control splice site choice in vivo have been identified. Here we describe a factor, Half pint (Hfp), that regulates RNA splicing in Drosophila.