Abstract
ABSTRACTThe anchor cell (AC) in C. elegans secretes an epidermal growth factor (EGF) homolog that induces adjacent vulval precursor cells (VPCs) to differentiate. The EGF receptor in the nearest VPC sequesters the limiting EGF amounts released by the AC to prevent EGF from spreading to distal VPCs. Here, we show that not only EGFR localization in the VPCs but also EGF polarity in the AC is necessary for robust fate specification. The AC secretes EGF in a directional manner towards the nearest VPC. Loss of AC polarity causes signal spreading and, when combined with MAPK pathway hyperactivation, the ectopic induction of distal VPCs. In a screen for genes preventing distal VPC induction, we identified sra-9 and nlp-26 as genes specifically required for polarized EGF secretion. sra-9(lf) and nlp-26(lf) mutants exhibit errors in vulval fate specification, reduced precision in VPC to AC alignment and increased variability in MAPK activation. sra-9 encodes a seven-pass transmembrane receptor acting in the AC and nlp-26 a neuropeptide-like protein expressed in the VPCs. SRA-9 and NLP-26 may transduce a feedback signal to channel EGF secretion towards the nearest VPC.
Highlights
Intercellular communication relies on the spatially and temporally controlled release of signaling molecules by signal-emitting cells
C. elegans vulval cell fate specification serves as an excellent in vivo model to analyze the subcellular localization of the epidermal growth factor (EGF) ligand and receptor at single cell resolution
It has been proposed that the limiting amounts of LIN-3 secreted by the anchor cell (AC) form a gradient that can act in a dose-dependent manner to specify the different fates of the proximal vulval precursor cells (VPCs) (Katz et al, 1995)
Summary
Intercellular communication relies on the spatially and temporally controlled release of signaling molecules by signal-emitting cells. Members of the epidermal growth factor (EGF) family are involved in a variety of cell fate decisions in all metazoans (Massagué and Pandiella, 1993). Many studies have focused on the mechanisms controlling the polarized secretion, M.K.M., 0000-0001-7862-8322; A.H., 0000-0002-4098-3721. Handling Editor: Susan Strome Received 14 January 2019; Accepted 4 May 2020 internalization and recycling of EGF receptors (Sorkin and Goh, 2008), less is known about the factors controlling the intracellular trafficking of the EGF family ligands. EGF ligands are typically produced as transmembrane precursor proteins They can either act as a membrane-bound form in a juxtacrine manner or be cleaved by intracellular rhomboid family proteases (Urban et al, 2001) and extracellular metalloproteases, allowing them to be released and signal at a distance (Massagué and Pandiella, 1993). One of the few examples demonstrating polarized EGF secretion during animal development in vivo is the release of the Drosophila EGF ligand Spitz by photoreceptor neurons (Yogev et al, 2010)
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