Asymmetric stem cell division contributes to tissue homeostasis by generating one stem cell and one differentiating cell. Asymmetric stem cell division can be achieved by asymmetric segregation of intrinsic fate determinants and/or asymmetric placement of daughter cells into different microenvironments (i.e., inside vs. outside of the stem cell niche, which specifies stem cell identity). Yet, the molecular and cellular mechanisms that govern asymmetric fate decision are poorly understood. It has long been known that asymmetries exist even in apparently symmetrically dividing cells. For example, during the final step of cytokinesis known as abscission, the resolution of the plasma membrane into two separate membranes normally occurs from only one side of the midbody, the structure that connects the two sister cells. This results in inheritance of the midbody ring (MR) by the cell on the other side. This asymmetry has been correlated with centrosome age;the daughter cell containing the mother centrosome inherits the MR remnant, suggesting that elaborate regulatory mechanisms control this process. However, in spite of these intriguing observations, it is not known whether these asymmetries have any biological relevance. We propose to investigate the mechanism and relevance of asymmetric MR inheritance during GSC cytokinesis, using Drosophila germline stem cells (GSCs), which offer a unique opportunity to investigate cellular asymmetries in the context of multicellular tissue architecture and development. Our preliminary study suggests that the MR inheritance during male and female GSCs is stereotypically asymmetric, which apparently involves asymmetry in centrosomal age and regulation of autophagy. We will investigate the underlying molecular mechanism and the biological relevance of this phenomenon, by examining the consequence(s) of defective MR inheritance. Lay summary:
We aim to understand the relevance of asymmetric cytokinesis during stem cell division. Results obtained from the proposed research may provide a means to manipulate stem cell behavior for therapeutic usage or inhibition of cancer growth.

Public Health Relevance

We aim to understand the relevance of asymmetric cytokinesis during stem cell division. Results obtained from the proposed research may provide a means to manipulate stem cell behavior for therapeutic usage or inhibition of cancer growth.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HD067692-02
Application #
8206777
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Ravindranath, Neelakanta
Project Start
2010-12-16
Project End
2013-05-31
Budget Start
2011-12-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2012
Total Cost
$233,250
Indirect Cost
$83,250
Name
University of Michigan Ann Arbor
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Salzmann, Viktoria; Chen, Cuie; Chiang, C-Y Ason et al. (2014) Centrosome-dependent asymmetric inheritance of the midbody ring in Drosophila germline stem cell division. Mol Biol Cell 25:267-75