PMID:23029159

Citation	Ruiz, OE, Nikolova, LS and Metzstein, MM (2012) Drosophila Zpr1 (Zinc finger protein 1) is required downstream of both EGFR and FGFR signaling in tracheal subcellular lumen formation. PLoS ONE 7:e45649
Abstract	The cellular and molecular cues involved in creating branched tubular networks that transport liquids or gases throughout an organism are not well understood. To identify factors required in branching and lumen formation of Drosophila tracheal terminal cells, a model for branched tubular networks, we performed a forward genetic-mosaic screen to isolate mutations affecting these processes. From this screen, we have identified the first Drosophila mutation in the gene Zpr1 (Zinc finger protein 1) by the inability of Zpr1-mutant terminal cells to form functional, gas-filled lumens. We show that Zpr1 defective cells initiate lumen formation, but are blocked from completing the maturation required for gas filling. Zpr1 is an evolutionarily conserved protein first identified in mammalian cells as a factor that binds the intracellular domain of the unactivated epidermal growth factor receptor (EGFR). We show that down-regulation of EGFR in terminal cells phenocopies Zpr1 mutations and that Zpr1 is epistatic to ectopic lumen formation driven by EGFR overexpression. However, while Zpr1 mutants are fully penetrant, defects observed when reducing EGFR activity are only partially penetrant. These results suggest that a distinct pathway operating in parallel to the EGFR pathway contributes to lumen formation, and this pathway is also dependent on Zpr1. We provide evidence that this alternative pathway may involve fibroblast growth factor receptor (FGFR) signaling. We suggest a model in which Zpr1 mediates both EGFR and FGFR signal transduction cascades required for lumen formation in terminal cells. To our knowledge, this is the first genetic evidence placing Zpr1 downstream of EGFR signaling, and the first time Zpr1 has been implicated in FGFR signaling. Finally, we show that down-regulation of Smn, a protein known to interact with Zpr1 in mammalian cells, shows defects similar to Zpr1 mutants.
Links	PubMed PMC3445489 Online version:10.1371/journal.pone.0045649
Keywords	Animals; Drosophila; Drosophila Proteins/physiology; Receptor Protein-Tyrosine Kinases/metabolism; Receptor, Epidermal Growth Factor/metabolism; Receptors, Fibroblast Growth Factor/metabolism; Repressor Proteins/physiology; Signal Transduction/physiology; Subcellular Fractions/enzymology; Subcellular Fractions/metabolism; Trachea/enzymology; Trachea/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
DROME:EGFR	involved_in	GO:0035149: lumen formation, open tracheal system	ECO:0000316: genetic interaction evidence used in manual assertion	FB:FBgn0003731	P		Seeded From UniProt	complete
DROME:FGFR2	involved_in	GO:0035149: lumen formation, open tracheal system	ECO:0000316: genetic interaction evidence used in manual assertion	FB:FBgn0003731	P		Seeded From UniProt	complete
DROME:SMN	involved_in	GO:0035149: lumen formation, open tracheal system	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q9W379	involved_in	GO:0035149: lumen formation, open tracheal system	ECO:0000316: genetic interaction evidence used in manual assertion	FB:FBgn0003731	P		Seeded From UniProt	complete
DROME:Q9W379	involved_in	GO:0007430: terminal branching, open tracheal system	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q9W379	involved_in	GO:0007173: epidermal growth factor receptor signaling pathway	ECO:0000316: genetic interaction evidence used in manual assertion	FB:FBgn0003731	P	part_of:(GO:0035149)	Seeded From UniProt	complete
DROME:Q9W379	involved_in	GO:0008543: fibroblast growth factor receptor signaling pathway	ECO:0000316: genetic interaction evidence used in manual assertion	FB:FBgn0285896	P	part_of:(GO:0035149)	Seeded From UniProt	complete
DROME:Q9VV74	involved_in	GO:0035154: terminal cell fate specification, open tracheal system	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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