The three aims of this project address the function of molecular asymmetries that occur very early in animal development, and the mechanisms by which they arise. Asymmetric cell division is essential for generation of cell-type diversity during differentiation and development. Failure o properly undergo asymmetric cell divisions can lead to defects in stem-cell renewal, tissue regeneration, and can contribute to carcinogenesis. We propose to use a near-ideal natural system, the early C. elegans embryo, to characterize the mechanisms of asymmetric distribution of cellular contents in specific blastomeres with modern genomic tools and analysis, followed by tests of function. Specifically, this proposal aims (1) to use blastomere-specific isolation, RNA- seq, and other high-throughput sequencing applications to comprehensively map RNA inheritance and transcriptional activity of seven invariant cell divisions in early C. elegans development, (2) to test the biological significance of asymmetric RNA segregation in development, and (3) to define the cis and trans-acting mechanisms required for asymmetric RNA segregation. To achieve these goals, we will also apply new approaches and technologies to the study of asymmetric segregation of cellular components. Our research plan is likely to identify cell-fate determinants and mechanisms that are generalizable to other systems, including humans.

Public Health Relevance

One of the earliest events in human development is the creation of asymmetry, or making one cell different from another. Generating asymmetry is important for the creation of different cell types during development, for example heart cells versus liver cells. This grant explores the molecular mechanisms that are behind the asymmetric distribution of cellular contents in the very earliest embryonic divisions and selected adult cell divisions. What we discover may help us understand human development, possibly leading to an increased understanding of birth defects and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM104050-02
Application #
8706912
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Hoodbhoy, Tanya
Project Start
2013-08-01
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$244,172
Indirect Cost
$54,172
Name
University of Chicago
Department
Genetics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637