Teresa Vales Orenic, PhD

Patterning of sensory organs in the Drosophila adult leg
Our research focuses on understanding the underlying mechanisms that generate the spatial organization of the many cell types found in multicellular organisms. With this goal in mind, we are investigating how sensory organs are patterned in the leg of the Drosophila melanogaster adult. Drosophila melanogaster has proven to be an ideal model system for study of the genetic regulation of pattern formation, due to the availability of a vast assortment of genetic and molecular tools. Significantly, it appears that the mechanisms used to pattern the Drosophila adult limbs are conserved in vertebrate limb development. Hence, study of these mechanisms in a model system such as Drosophila will provide insights for development of future therapies for human diseases and genetic disorders.

The sensory organs (bristles) of Drosophila adult legs are precisely organized into a series of eight longitudinal rows. In pupal legs, expression of the proneural gene, achaete (ac), in eight longitudinal stripes defines the primordia of the leg bristle rows. This pattern of ac expression is established in part through the function of the basic-helix-loop (bHLH) protein, Hairy (H), which in pupal legs is expressed in four longitudinal stripes positioned between alternating pairs of ac stripes. Two longitudinal stripes are expressed along the dorsal/ventral (D/V) axis of the leg disc (D/V-h stripes), and the other two traverse the anterior/posterior (A/P) axis (A/P-h stripes). In the absence of h function, ac expression expands into the regions normally occupied by h, resulting in disorganized bristle rows in the adult.

Understanding of how bristle row pattern is produced in the Drosophila leg, hinges on elucidation of the mechanisms responsible for spatially regulating the longitudinal stripes of h and ac expression in the leg. We have found that h expression along the D/V axis is directed by dorsal and ventral specific enhancers which integrate signals from the Hedgehog (Hh), Decapentaplegic (Dpp), and Wingless (Wg) pathways. D/V-h expression is regulated through a non-linear pathway in which the downstream effector of Hh, Cubitus interruptus (Ci) plays a dual role. In addition to serving as an upstream activator of dpp and wg expression, Ci acts combinatorially with the downstream effectors of Wg and Dpp, Mothers against dpp (Mad) and dTCF, to activate D/V-h expression. We are currently pursuing DNA binding and mutational analyses of the D/V-h enhancers.

A second project involves the regulation of the A/P-h stripes. While the regulation of D/V-h can be easily placed into the patterning events occurring across the A/P compartment boundary, A/P-h is expressed orthogonal to this landmark. A study of A/P-h regulation should provide interesting insights into long range signaling events and how topology influences gene expression. Our studies indicate that spatial regulation of A/P-h is mediated at least in part by Dpp and Wg. The boundaries of A/P-h expression are set up via repression dorsally and ventrally by Dpp and Wg, respectively. We are pursuing genetic and molecular studies aimed at identifying the factors that mediate repression of A/P-h by Dpp and Wg and that regulate the temporal coordination of A/P-h expression.

To complete our understanding of how leg sensory bristles are patterned, we are furthering our studies on the regulation of ac leg expression. Our goal is to distinguish between two possible models by which ac leg expression is established: a) that ac expression is uniformly activated and the 8 stripes are established through negative regulation by h and another gene that functions in a manner similar to h or b) that ac expression is established in four domains in response to earlier patterning events, such as those that regulate h expression.

(Complete list of publications on Google Scholar)

1. Takaesu, N.T., Bulanin, D.S., Orenic, T.V. and Newfeld, S.J. (2008) A combinatorial enhancer recognized by Mad, dTCF and Brinker is required for dpp function in the Drosophila posterior spiracle. Dev. Biol. 313: 829-843.
2. Shroff, S., Joshi, M. and Orenic, T.V. (2007) Differential Delta expression underlies the diversity of bristle patterns among the Drosophila legs. Mech. Dev. 124(1), p. 43-58
3. Joshi, M., Buchanan, K., Shroff, S. and Orenic, T.V. (2006) Delta and Hairy establish a periodic prepattern that positions sensory bristles in Drosophila legs. Dev. Biol. 293(1), p. 64-76.
4. Kwon, C., Hays, R., Fetting, J., Orenic, T.V. (2004). Opposing inputs by Hedgehog and Brinker define a stripe of hairy expression in the Drosophila leg imaginal disc. Development 131, p. 2681.
5. Hays , R., Buchanan, K.T., Neff, C. and Orenic, T.V. (1999). Patterning of leg sensory organs through combinatorial signalling by Hedgehog, Decapentaplegic and Wingless. Development 126, 2891.
6. Hepker, J., Wang, Q.T., Motzny, C., Holmgren, R. and Orenic, T.V. (1997). Drosophila cubitus interruptus forms a negative feedback loop with patched and regulates expression of Hh target genes. Development 124, 549-558.

PhD, Northwestern University

BS, Barry University