Building: Arthur and Rochelle Belfer Building for Biomedical Research

Tel: 972-8-934-2426

Fax: 972-8-934-4108

e-mail: Talila.Volk@weizmann.ac.il

Heterotypic intercellular interactions are the basis for organ and complex tissue formation. We are studying how muscles become associated with their specific tendon cells, during Drosophila embryogenesis. We discovered that the pathfinding of myotubes towards their target attachment cells in the ectoderm follows a characteristic reciprocal molecular cross-talk mechanism.

While the epidermal muscle attachment cells provide the information required for guiding the myotubes towards their correct locations, myotubes are instrumental for induction of terminal differentiation of the attachment cells into mature tendon cells. The end result of this process is that each myotube is anchored at both ends to a single tendon cell.

The transcription factor Stripe, a key regulator of differentiation of the epidermal muscle attachment cells, is required twice in the course of tendon cell differentiation; during early developmental stages it induces ectodermal cells to become competent epidermal muscle attachment (EMA) cells, while following muscle binding it mediates, together with the bHLH protein Delilah, terminal differentiation of these cells into tendon cells. The muscle-dependent differentiation of the tendon cells is mediated by Vein, a neuregulin-like growth factor, which is secreted from the approaching muscle and non-autonomously induces tendon cell differentiation, by activation of the EGF receptor pathway in the tendon cell.

Vein localization at the muscle-tendon junctional site is mediated by Kakapo, a cytoskeletal-associated protein. Who, a putative RNA-binding protein functions as a repressor of the Vein-induced differentiation of tendon cells.

Our goal is to characterize the specific role of each of these proteins in the process of Vein-induced tendon cell differentiation, and to identify additional molecular components essential for that process.

References

Volk, T. and VijayRaghavan, K. (1994). A central role for epidermal segment border cells in the induction of muscle patterning in the Drosophila embryo. Development 120: 59-70. PDF Version

Yarnitzky, T. and Volk, T. (1995). Laminin is required for heart, somatic muscles and gut development, in the Drosophila embryo. Dev. Biol. 169:609-618. PDF Version

Frommer, G., Vorbruggen, G., Pasca, G., Jackle, H. and Volk, T. (1996) Epidermal egr-like zinc finger protein of Drosophila participates in myotube guidancet. EMBO J. 15:1642-1649.

Rosenberg-Hasson, Y., Renert-Pasca, M. and Volk, T. (1996) A Drosophila Dystrophin-related protein, MSP-300, is required for embryonic muscle morphogenesis. Mech. of Dev. 65:83-94. PDF Version

Beiman, M., Shilo, B-Z. and Volk, T.(1996) Heartless, a Drosophila FGF receptor homologue, is essential in the mesoderm for cell migration and establishment of several lineages. Genes and Dev. 10:2993-1002.

Becker, S., Pasca, G., Strumpf, D., Min, L. and Volk, T. (1997) Reciprocal signaling between Drosophila epidermal muscle attachment cells and their corresponding muscles. Development. 124: 2615-2622. PDF Version

Yarnitzky, T., Min, L. and Volk, T. (1997) The Drosophila neuregulin-homologue, Vein, mediates inductive interactions between myotubes and their epidermal attachment cells. Genes and Dev. 11: 2691-2700. PDF Version

Yarnitzky, T., Min, L. and Volk, T. (1998) An interplay between two EGF-receptor ligands, Vein and Spitz, is required for the formation of a subset of muscle precursors in Drosophila. Mech. Dev. 79:73-82. PDF Version

Strumpf, D. and Volk, T. (1998) Kakapo, a novel cytoskeletal-associated protein is essential for the restricted localization of the neuregulin-like factor, Vein, at the muscle-tendon junction site. J. Cell Biol. 143:1259-1270. PDF Version

Volk, T. (1999) Signaling out Drosophila tendon cells: a dialogue between two distinct cell types. Trends. Genet. 15:448-453. PDF Version

Nabel-Rosen, H, Dorevitch, N., Reuveny, A. and Volk, T. (1999) The balance between two isoforms of the Drosophila RNA-binding protein how controls tendon cell differentiation. Mol. Cell. 4:573-584. PDF Version

Neuman, S., Kaban, A., Volk, T., Yaffe, D. and Nudel, U. (2001) The dystrophin / utrophin homologues in Drosophila and in sea urchin. Gene. 263:17-29. PDF Version

Nabel-Rosen, H, Volohonsky, G., Reuveny, A., Zaidel-Bar, R. and Volk, T. (2002) Two isoforms of the Drosophila RNA binding protein, how, act in opposing directions to regulate tendon cell differentiation. Dev. Cell. 2:183-193. PDF Version