ELUCIDATION OF THE ROLE OF BREATHLESS, A DROSOPHILA FGF RECEPTOR HOMOLOG, IN TRACHEAL CELL-MIGRATION

DFGF-R1 (breathless), a Drosophila FGF receptor homolog, is required f or the migration of tracheal cells and the posterior midline glial cel ls during embryonic development. To define the role of this receptor i n cell migration, we have monitored the biological effects of a deregu lated receptor containing the extracellular and transmembrane regions of the torso dominant allele and the cytoplasmic domain of DFGF-R1. Ub iquitous expression of the chimeric receptor at the time of tracheal c ell migration did not disrupt migration in wild-type embryos. However, induction of the chimeric receptor corrected the tracheal defects of breathless (btl) mutant embryos, allowing the tracheal cells to migrat e along their normal tracts. This result indicates that the normal act ivity of DFGF-R1 in promoting cell migration does not require spatiall y restricted cues. Late inductions of the chimeric construct, after th e normal initiation of tracheal migration, allowed the definition of a broad time window during which the external signals guiding migration persist and the tracheal cells retain the capacity to respond to thes e cues. Rescue of tracheal migration in btl mutant embryos by the chim eric construct provides a sensitive biological assay for the activity of other Drosophila receptor tyrosine kinases (RTKs). Deregulated rece ptors containing the cytoplasmic domains of DFGF-R2, DER, torso, and s evenless were all able to partially rescue the migration defects. Cons istent with the notion that these RTKs share a common signaling pathwa y, constructs containing the activated downstream elements Dras1 and D raf were also able to rescue tracheal migration, demonstrating that th ese two proteins are key players in the DFGF-R1 signaling pathway.