title: A role of the LIN-12/Notch signaling pathway in diversifying the non-striated egg-laying muscles in C. elegans.
abstract: The proper formation and function of an organ is dependent on the specification and integration of multiple cell types and tissues. An example of this is the Caenorhabditis elegans hermaphrodite egg-laying system, which requires coordination between the vulva, uterus, neurons, and musculature. While the genetic constituents of the first three components have been well studied, little is known about the molecular mechanisms underlying the specification of the egg-laying musculature. The egg-laying muscles are non-striated in nature and consist of sixteen cells, four each of type I and type II vulval muscles and uterine muscles. These 16 non-striated muscles exhibit distinct morphology, location, synaptic connectivity and function. Using an RNAi screen targeting the putative transcription factors in the C. elegans genome, we identified a number of novel factors important for the diversification of these different types of egg-laying muscles. In particular, we found that RNAi knockdown of lag-1, which encodes the sole C. elegans ortholog of the transcription factor CSL (CBF1, Suppressor of Hairless, LAG-1), an effector of the LIN-12/Notch pathway, led to the production of extra type I vulval muscles. Similar phenotypes were also observed in animals with down-regulation of the Notch receptor LIN-12 and its DSL (Delta, Serrate, LAG-2) ligand LAG-2. The extra type I vulval muscles in animals with reduced LIN-12/Notch signaling resulted from a cell fate transformation of type II vulval muscles to type I vulval muscles. We showed that LIN-12/Notch was activated in the undifferentiated type II vulval muscle cells by LAG-2/DSL that is likely produced by the anchor cell (AC). Our findings provide additional evidence highlighting the roles of LIN-12/Notch signaling in coordinating the formation of various components of the functional C. elegans egg-laying system. We also identify multiple new factors that play critical roles in the proper specification of the different types of egg-laying muscles.
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.
authors: Jared J
authors: JJ
authors: Hale
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.
authors: Nirav M
authors: NM
authors: Amin
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.
authors: Carolyn
authors: C
authors: George
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.
authors: Zachary
authors: Z
authors: Via
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.
authors: Herong
authors: H
authors: Shi
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States. Electronic address: JL53@cornell.edu.
authors: Jun
authors: J
authors: Liu
mesh_terms: D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D005260:Female; D057850:Hermaphroditic Organisms / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D008297:Male; D009132:Muscles / Q000378:metabolism*; D010058:Oviposition / Q000502:physiology*; D034622:RNA Interference; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014844:Vulva / Q000166:cytology / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D008024:Ligands; C082460:Lin-12 protein, C elegans; D051880:Receptors, Notch; D014157:Transcription Factors
keywords: C. elegans; Mesoderm; Non-striated muscle; Notch; Vulval muscle; lag-1; lag-2; lin-12; sel-12; sel-8