Abstract:
Drosophila Caspar (Casp) is an ortholog of mammalian Fas associated factor
1 (FAF1). Analysis of the primary sequence suggests that the protein maintains its
function between flies and humans. Casp in flies has been studied in the context of
host defence, with Casp negatively regulating the Immune Deficient (IMD) pathway, by
modulating activity of Dredd, an endo-protease that cleaves and activates
RELISH/NFκB in immune signaling.
In Drosophila, casp is expressed ubiquitously throughout development, with
females also depositing maternal casp mRNA in the developing oocyte. In our study
, we find that casp is a maternal effect gene, with an essential developmental
requirement in the 0-3 hour embryo. We prove maternal roles by demonstrating that
paternal zygotic expression cannot rescue embryonic lethality due to maternal loss
of function (lof) of casp. Maternal casp lof embryos die in stages 8-15, suggesting
that Casp in the early embryo performs critical functions that when absent stalls
embryogenesis immediately post gastrulation. We are currently using antibodies and
in-situ probes to understand cellular roles for Casp.
Caspar/FAF1 contains domains for interactions with p97/VCP and poly-
ubiquitin suggesting molecular functions in the ubiquitin-proteasomal degradative
pathway. We hypothesize that the developmental stalling is a consequence of
aberrant degradation of maternal proteins during the maternal to zygotic transition.
