Abstract
Dorsal closure (DC) is a developmental process in which two contralateral epithelial sheets migrate to seal a large hole in the dorsal ectoderm of the Drosophila embryo. Two signaling pathways act sequentially to orchestrate this dynamic morphogenetic process. First, c-Jun N-terminal kinase (JNK) signaling activity in the dorsal-most leading edge (LE) cells of the epidermis induces expression of decapentaplegic (dpp). Second, Dpp, a secreted TGF-β homolog, triggers cell shape changes in the adjacent, ventrally located lateral epidermis, that guide the morphogenetic movements and cell migration mandatory for DC. Here we uncover a cell non-autonomous requirement for the Epidermal growth factor receptor (Egfr) pathway in the lateral epidermis for sustained dpp expression in the LE. Specifically, we demonstrate that Egfr pathway activity in the lateral epidermis prevents expression of the gene scarface (scaf), encoding a secreted antagonist of JNK signaling. In embryos with compromised Egfr signaling, upregulated Scaf causes reduction of JNK activity in LE cells, thereby impeding completion of DC. Our results identify a new developmental role for Egfr signaling in regulating epithelial plasticity via crosstalk with the JNK pathway.
Highlights
Epithelial sheet fusion and collective cell migration are key processes in normal development, wound healing and pathogenesis [1,2]
dorsal closure (DC) is known to require the coordinated action of two signaling pathways: (i) the c-Jun N-terminal kinase (JNK) pathway, which is activated in the dorsalmost leading edge (LE) cells of the migrating epithelia; and (ii) the Decapentaplegic (Dpp) pathway, induced by the JNK pathway, which signals to neighboring lateral epidermis cells to drive the cellular changes required for DC
We uncover a new tier of regulation essential for DC, mediated by the Epidermal growth factor receptor (Egfr) pathway
Summary
Epithelial sheet fusion and collective cell migration are key processes in normal development, wound healing and pathogenesis [1,2]. One system that has offered fundamental insights into the mechanisms controlling epithelial dynamics and cell migration is the embryonic process of dorsal closure (DC) in Drosophila melanogaster. In this developmental setting, two contralateral epithelial sheets from opposing sides of the embryo migrate and converge at the dorsal midline above the amnioserosa (AS), an extraembryonic epithelium tissue, thereby generating a continuous epidermis that seals a large dorsal hole (Fig 1A) [3]. C-Jun N-terminal kinase (JNK) pathway activity in the dorsal-most leading edge (LE) cells induces expression of the gene decapentaplegic (dpp), encoding the TGF-β/BMP family member Dpp [4,5,6]. DC is an excellent experimental model system with which to identify and characterize the signaling events regulating complex movements of epithelial layers
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