Coalescence of the embryonic gonad in Drosophila melanogaster requires directed migration of the primordial germ cells (PGCs) towards the somatic gonadal precursor cells (SGPs). It was recently proposed that an ATP-Binding Cassette (ABC) transporter, Mdr49, functions in the embryonic mesoderm to facilitate the transmission of the PGC attractant from the SGPs; however, the precise molecular identity of the mdr49 dependent guidance signal remained elusive. Employing the ‘loss’ and ‘gain’ of function strategies we show that mdr49 is a component of the hh pathway and it potentiates the signaling activity. This function is direct as, in mdr49 mutant embryos, Hh ligand is inappropriately sequestered in the hh expressing cells. Our data also suggest that role of Mdr49 is to provide cholesterol for the correct processing of the Hh precursor protein. Supporting this conclusion, PGC migration defects in mdr49 embryos are substantially ameliorated by a cholesterol-rich diet.
Functioning of an ABC transporter, Mdr49, in Hh signaling and germ cell migration
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Girish Deshpande, Diane Manry, Nicholas Jourjine, Vladic Mogila, Henny Mozes, Tzofia Bialistoky, Offer Gerlitz, Paul Schedl; Functioning of an ABC transporter, Mdr49, in Hh signaling and germ cell migration. Development 2016; dev.133587. doi: https://doi.org/10.1242/dev.133587
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