AdfR functions downstream of twist to control mesoderm development. G. Zimmermann¹, E.E. Furlong², M.P.S. Scott¹. 1) Dept. of Developmental Biology, Stanford University; 2) Developmental Biology Programme, EMBL.

   Our work investigates the genetic hierarchies that control muscle development during Drosophila embryogenesis. All muscle tissues are derived from the mesoderm, which is formed during gastrulation from the ventral-most cells of the blastoderm-stage embryo. Twist, a basic helix-loop-helix transcriptional activator, is a master regulator that controls the expression of mesoderm-specific genes and thus lies at the top of the myogenic regulatory hierarchy. Our goal is to identify and characterize the regulatory mechanisms that function downstream of twist to specifically control myogenesis.
    We have identified a novel target of Twist (adfR - Alcohol Dehydrogenase Factor 1 Related) that encodes a putative transcription factor essential for normal muscle development. AdfR belongs to a large family of 46 Drosophila proteins predicted to contain a MADF domain. These domains were previously shown to bind DNA directly. We show that AdfR is a nuclear protein first expressed in the presumptive mesoderm during late gastrulation. At later stages, the protein is expressed in the central (brain and ventral nerve cord) and peripheral nervous systems, suggesting that it may also have regulatory functions in the formation of these tissues. AdfR is expressed in equivalent cell types during imaginal disk development (wing-disk myoblasts and eye-disk neurons). Depletion of the adfR transcript through RNAi causes severe embryonic defects leading to a disorganized mesoderm and early developmental arrest. The majority of these embryos do not secrete a cuticle or denticle belts. Early overexpression of adfR causes developmental arrest during germband retraction. Disrupting the expression of adfR in imaginal disks through either RNAi or overexpression also blocks the formation of adult structures. We are currently characterizing the molecular functions and transcriptional targets of adfR during the development of both the mesoderm and the nervous system.