Abstract
ABSTRACTMEF2 (myocyte enhancer factor 2) transcription factors are found in the brain and muscle of insects and vertebrates and are essential for the differentiation of multiple cell types. We show that in the fruit fly Drosophila, MEF2 is essential for the formation of mushroom bodies in the embryonic brain and for the normal development of wings in the adult. In embryos mutant for mef2, there is a striking reduction in the number of mushroom body neurons and their axon bundles are not detectable. The onset of MEF2 expression in neurons of the mushroom bodies coincides with their formation in the embryo and, in larvae, expression is restricted to post-mitotic neurons. In flies with a mef2 point mutation that disrupts nuclear localization, we find that MEF2 is restricted to a subset of Kenyon cells that project to the α/β, and γ axonal lobes of the mushroom bodies, but not to those forming the α’/β’ lobes.
Highlights
Gene duplications can lead to functional variations among family members, thereby driving increased cell-type diversity (Arendt, 2008) and evolutionary pressure to maintain replicates (Assis and Bachtrog, 2013)
The insertions sites were independent, they were clustered into two regions with those closest to mef2 showing preferential β–galactosidase activity in the mushroom body (MB) and antennal lobes and those farther away showing additional expression throughout the cortex of the central brain and the optic lobes (Fig. S1)
Nuclear retention signal for MEF2 Mammalian MEF2 contains several sequences near the C-terminus that are required for its nuclear localization, but these sequences are not conserved in Drosophila and the MEF2 nuclear localization sequence has not been identified (Yu, 1996; Borghi et al, 2001)
Summary
Gene duplications can lead to functional variations among family members, thereby driving increased cell-type diversity (Arendt, 2008) and evolutionary pressure to maintain replicates (Assis and Bachtrog, 2013). The MEF2 family of transcription factors has been assigned a myriad functions ranging from the differentiation of multiple cell lineages during development, to cellular stress response and neuronal plasticity in adulthood. Mef in Drosophila is critical for the differentiation of multiple muscle cell lineages and is essential for viability (Lilly et al, 1995; Lin et al, 1997; Potthoff and Olson, 2007). The DNA sequences bound by MEF2 are evolutionarily conserved and MEF2 has been shown to activate transcription of orthologous gene sets in flies and mice (Bour et al, 1995; Lilly et al, 1995; Ranganayakulu et al, 1995; Lin et al, 1997; Potthoff and Olson, 2007). We examine the expression of MEF2 in the developing MB and among subsets of Kenyon cells in the adult fly, and evaluate MB formation and phenotypes in mef mutant alleles
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