CELL DIVISION PATTERNING DURING DEVELOPMENT

Project: Research project

Project Details

Description

DESCRIPTION: The proposed experiments focus on the dally gene which encodes
a GPI linked cell surface proteoglycan in Drosophila. Proteins in this
class are thought to associate with growth factors and may function as
co-receptors. The dally gene was initially identified in Drosophila because
hypomorphic mutations caused a delay in certain mitotic division in the eye
disc and in the lamina precursors of the brain. Associated with these cell
cycle defects is a failure to repress G1 cyclins (A and possibly E) such
that they persist into M phase. Selleck shows that reductions in cyclinA
dosage partially rescues the mitotic arrest, suggesting that the dal
phenotype is a consequence of this expression.

In the present proposal, Selleck wishes to test a specific hypothesis,
namely that dally acts as a co-receptor for the BMP like growth factor dpp
and that local synthesis of that growth factor is what controls the pattern
of division. Dally would therefore provide a unique handle on the role of
Glypicans in the reception of growth factor signals. In addition to the
production of antibodies to dally and the biochemical characterization of
its cell surface linkage and structure function, most of the proposal
focuses on the interaction between dal and the dpp pathway. Some of these
studies will be carried out on the wing disc where downstream molecular
marker for dpp reception (I. e., omb and sal gene) are available and have
been well characterized. Others investigate whether simultaneous expression
of dal alters a cell's sensitivity to ectopic dpp expression. Selleck will
also continue his characterization of the relationship between dal and cell
cycle regulators, particularly the mechanisms underlying the persistence of
cyclin E in metaphase. Tests for direct physical interactions between dal
and dpp will be carried out using radiolabeled dpp and the previously
obtained antibodies to dal, or co-electrophoresis. Mutagenesis screens are
proposed to obtain true null alleles of dal by screening in the presence of
a duplication to counter the potential haplo-lethality of the locus.
StatusFinished
Effective start/end date4/1/973/31/98

Funding

  • National Institute of General Medical Sciences

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