It is believed that cleavage stage events restrict cell fate because experimental manipulation of blastomeres alters terminal cell differentiation. However, the manipulated blastomeres may exhibit different fates only because their progeny are affected differently by the inductive interactions that occur soon before terminal differentiation. Specific cleavage stage events have never studied directly because blastomere-specific characteristics have not been identified heretofore. However, I have demonstrated recently that blastomeres of the frog Xenopus laevis whose progeny have different fates synthesize different amounts of particular proteins beginning at the 16-cell stage; these protein synthetic differences are the earliest cell-specific properties that have been identified. I propose to study cleavage stage determinative events directly by examining whether interactions between blastomeres produce this blastomere- specific protein synthetic pattern. This pattern will be examined after excising a blastomere's neighbors, exchanging its neighbors, culturing it in isolation or in combination with other blastomeres. Blastomeres whose protein synthetic patterns are altered by these manipulations will be subjected to a lineage analysis to examine whether these interactions and these proteins are involved in cell lineage determination. If these manipulations alter the protein synthetic pattern, I will conclude that cleavage stage cellular interactions produce blastomere-specific properties. These results will support the hypothesis that cell fate is restricted by cleavage stage events. If these manipulations do not affect the blastomere-specific protein synthetic patterns, I will conclude that blastomere-specific properties are acquired independent of cellular interactions. These studies are unique because they allow direct monitoring of changes due to manipulations that alter cellular interactions at very early embryonic stages and because the effects of these manipulations can be compared directly to changes in a cell's fate.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HD023324-03
Application #
3469664
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1987-08-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904