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PMID:23029159

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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

Significance

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

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

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

See also

References

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