For asymmetric divisions to proceed properly, stem cells must accomplish the following: A) establish proper polarity, B) build a functional mitotic spindle using centrosomes that steer and anchor it, and C) properly align the spindle along a defined polarity axis using forces generated by astral MTs-cortical interactions. If executed properly, stem cells divide asymmetrically to produce a differentiating daughter cell. However, defects in this process lead to missegregation of cell fate determinants. If both cells retain stem cell identity, this can, under certain circumstances, lead to tumorogenesis. Mutations in polarity genes (Lgl, Dlg, Scrib) cell fate determinants (Pros, Numb, Mira, Brat), and centrioles/centrosomes (sas-4, asl, aurora A, polo) can all lead to cell overgrowth and malignant transformation. Our lab is interested understanding a unique feature of stem cell asymmetric division the asymmetric activity of the two centrosomes. To investigate how this asymmetry is achieved we are determining the protein composition of the two centrioles/centrosomes. Preliminary data suggest that the composition does differ in several waysthe presence of Polo on the active centrosome and the presence of Centrobin on the inactive centrosome in interphase. Further investigation is underway to analyze all the centriole proteins, and some centrosome components. For this project it was necessary to establish protocols for proper live cell imaging of two SC populations, the neural SCs and the germline SCs. We are now able to follow our SCs for 48hrs with little damage to the tissue and cells. We are currently analyzing both SC populations in wild-type and mutant centrosome backgrounds to determine how specific mutations alter SC division and function.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2011
Total Cost
$801,743
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
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Lerit, Dorothy A; Shebelut, Conrad W; Lawlor, Kristen J et al. (2017) Germ Cell-less Promotes Centrosome Segregation to Induce Germ Cell Formation. Cell Rep 18:831-839
Varadarajan, Ramya; Hammer, John A; Rusan, Nasser M (2017) A centrosomal scaffold shows some self-control. J Biol Chem 292:20410-20411
Galletta, Brian J; Jacobs, Katherine C; Fagerstrom, Carey J et al. (2016) Asterless is required for centriole length control and sperm development. J Cell Biol 213:435-50
Schoborg, Todd A; Rusan, Nasser M (2016) Taking Centrioles to the Elimination Round. Dev Cell 38:10-2
Lerit, Dorothy A; Jordan, Holly A; Poulton, John S et al. (2015) Interphase centrosome organization by the PLP-Cnn scaffold is required for centrosome function. J Cell Biol 210:79-97
Pronobis, Mira I; Rusan, Nasser M; Peifer, Mark (2015) A novel GSK3-regulated APC:Axin interaction regulates Wnt signaling by driving a catalytic cycle of efficient ?catenin destruction. Elife 4:e08022
Schoborg, Todd; Zajac, Allison L; Fagerstrom, Carey J et al. (2015) An Asp-CaM complex is required for centrosome-pole cohesion and centrosome inheritance in neural stem cells. J Cell Biol 211:987-98
Smyth, Jeremy T; Schoborg, Todd A; Bergman, Zane J et al. (2015) Proper symmetric and asymmetric endoplasmic reticulum partitioning requires astral microtubules. Open Biol 5:
Lerit, Dorothy A; Plevock, Karen M; Rusan, Nasser M (2014) Live imaging of Drosophila larval neuroblasts. J Vis Exp :
Galletta, Brian J; Guillen, Rodrigo X; Fagerstrom, Carey J et al. (2014) Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies. Mol Biol Cell 25:2682-94

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