Research in the Laboratory of Leon W. Browder
I am engaged in a collaboration with Dr. Robert S. Winning, Eastern Michigan University, on the function of a receptor tyrosine kinase, Pagliaccio (Pag), in embryonic development of the South African Clawed Frog, Xenopus laevis. Pag, which was cloned by Dr. Winning, is expressed in involuting mesoderm during gastrulation and later in the developing central nervous system and cranial neural crest. This receptor is a member of the Eph class of tyrosine kinases, some members of which have been implicated in axon guidiance. We propose to test the hypothesis that Pag plays a similar role by guiding the migrating cranial neural crest in amphibian embryos by using the transgenesis procedure of Kroll and Amaya to produce embryos that express antisense Pag. If Pag is involved in guiding migration of cranial neural crest cells, expression of antisense Pag should disrupt migration.
I am also involved in a collaboration with Caren Helbing, Karl Riabowol and Randal Johnston, University of Calgary, on the function of an tumor suppressor gene called ING1. Overexpression of ING1 confers sensitivity to apoptosis in mammalian cells, whereas decreased ING1 expression protects cells from apoptosis. Likewise, suppression of ING1 results in neoplastic transformation (Garkavtsev et al., 1996; Helbing et al., 1997).
An ING1 protein (p33^ING1) is expressed in regressing tails of metamorphosing Xenopus tadpoles (Helbing et al., 1997). This suggests that ING1 may be involved in regulating programmed cell death during Xenopus development. We will test this hypothesis by using the transgenesis procedure to produce tadpoles that express antisense ING1. If ING1 is necessary for programmed cell death during development, expression of antisense ING1 should prevent PCD from occurring.
Garkavtsev et al. 1996. Suppression of the novel growth inhibitor ING1 promotes neoplastic transformation. Nature Genetics 14: 415-420.
Helbing et al. 1997. A novel candidate tumor suppressor, ING1, is involved in the regulation of apoptosis. Cancer Res. 57: 1255-1258.
Kroll, K.L. and Amaya, E. 1996. Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation. Development 122: 3173-3183.
Winning et al. 1996. Disruption of cell adhesion in Xenopus embryos by Pagliaccio, an Eph-class receptor tyrosine kinase. Developmental Biology 179: 309-319.
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