Abstract
Although the molting cycle is a hallmark of insects and nematodes, neither the endocrine control of molting via size, stage, and nutritional inputs nor the enzymatic mechanism for synthesis and release of the exoskeleton is well understood. Here, we identify endocrine and enzymatic regulators of molting in C. elegans through a genome-wide RNA-interference screen. Products of the 159 genes discovered include annotated transcription factors, secreted peptides, transmembrane proteins, and extracellular matrix enzymes essential for molting. Fusions between several genes and green fluorescent protein show a pulse of expression before each molt in epithelial cells that synthesize the exoskeleton, indicating that the corresponding proteins are made in the correct time and place to regulate molting. We show further that inactivation of particular genes abrogates expression of the green fluorescent protein reporter genes, revealing regulatory networks that might couple the expression of genes essential for molting to endocrine cues. Many molting genes are conserved in parasitic nematodes responsible for human disease, and thus represent attractive targets for pesticide and pharmaceutical development.
Highlights
Ecdysozoan animals, including nematodes and arthropods [1], develop through periodic larval stage molts when the exoskeleton is shed and synthesized anew
Gene annotations as well as spatial and temporal expression studies suggest that many genes identified here specify transmembrane proteins, secreted enzymes, and structural components of the cuticle that are synthesized in epithelial cells and likely regulate the de novo production or release of the exoskeleton at each molt
Fusions to green fluorescent protein (GFP) show that expression of several genes uncovered in this screen cycles in phase with molting, similar to the expression of genes encoding particular nuclear hormone receptor (NHR) and cuticle collagens [68,69]
Summary
Ecdysozoan animals, including nematodes and arthropods [1], develop through periodic larval stage molts when the exoskeleton is shed and synthesized anew. The neuropeptide prothoracicotropic hormone stimulates synthesis of ecdysone in the prothoracic glands [3]. At the end of each larval stage, the neuropeptide eclosion hormone, combined with a decline in the titer of ecdysone, prompts release of the peptide ecdysistriggering hormone from glands lining the trachea [4,5,6,7]. Environmental cues, including photoperiod, temperature, and humidity, as well as physiologic factors, including size, stage, and the nutritional status of the organism, modulate secretion of prothoracicotropic hormone in various arthropods, suggesting extensive sensory input to the neuroendocrine secretions that govern molting [3]. Little is known about the circuits that initiate, terminate, or set the pace of the molting cycle in any Ecdysozoan
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