Screening for mutations that affect the epidermal cuticle pattern has been used as a powerful approach to identify genes involved in developmental decisions and signaling pathways (Luschnig et al., 2004; Mayer and Nusslein-Volhard, 1988; Nusslein-Volhard and Wieschaus, 1980). Some years ago, it became clear that the finer details of cuticle pattern, specifically the column-specific differences in denticle shape and hook orientation, occurred as a result of differential activation of the signaling pathways that pattern the epidermis (Alexandre et al., 1999). Since that time, no downstream targets have been identified that selectively affect denticle shape or hooking, and the mechanism(s) involved have remained elusive. Here, we show that the transcription factor stripe integrates signaling information and positional cues to specify multiple aspects of this column-specific denticle pattern, including denticle density and anterior hook orientation. Further, we show that stripe governs hook orientation, in part, via up-regulation of the spectraplakin shot, which functions both cell autonomously and cell non-autonomously to specify denticle hook orientation via interaction with the microtubule cytoskeleton. Thus, the stripe-shot circuit has the potential to link the un-patterned blastoderm to a fully patterned ventral cuticle. It appears that the non-autonomous stripe-shot circuit culminates in the localization of Shot protein across the boundaries where denticle hooks reverse. As spectraplakins can stabilize, localize and bundle microtubule arrays, as well as create specialized membrane domains via membrane protein clustering (Leung et al., 1999; Roper et al., 2002; Sanchez-Soriano, 2009), a likely hypothesis is that Shot organizes a specialized microtubule array or other cytoskeletal complex at these interfaces.
Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 2010. Source: Dissertation Abstracts International, Volume: 71-12, Section: B, page: 7342. Adviser: Stephen Dinardo.