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Cell Type Choice
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How can a group of undifferentiated cells break symmetry and become different cell types? If the cells are at different phases of the cell cycle a signal can tell them to look at what phase they happen to be in and this will determine their initial fate.

 

In wild-type, prestalk cells originate from cells in S phase or early G2 at starvation, while in rtoA they originate randomly from cells in any phase of the cell cycle. 

Wild-type

rtoA

 

In Dictyostelium, initial cell type choice is correlated with the cell-cycle phase of the cell at the time of starvation.  For each pair of sister cells which happen to be in S or early G2 phase (Dictyostelium does not have a G1 phase) when they starve, one sister differentiates into a prestalk cell while the other sister becomes a null cell (a cell that does not express either a characteristic prestalk or a prespore antigen). Cells starved in late G2 or M phase similarly differentiate into either a prespore or a null cell. We have isolated a mutant, ratioA (rtoA), with a defect in this mechanism that results in an abnormally high percentage of prestalk cells. The cell cycle is normal in rtoA. In the wild type, prestalk cells differentiate from those cells in S or early G2 phase at starvation and prespore cells from cells in late G2 or M phase at starvation. In rtoA mutants, both prestalk and prespore cells originate randomly from cells in any phase of the cell cycle at starvation.  Through further work  we have found that rtoA cells have a defect in the fusion of endocytic vesicles. They also have a decreased exocytosis rate, a decreased pH of endocytic/exocytic vesicles, and an increased average cytosolic pH. Our data indicate that the serine-rich domain of RtoA can mediate membrane fusion and that RtoA can increase the rate of vesicle fusion during processing of endoctyic vesicles. We hypothesize that RtoA modulates initial cell type choice by linking vegetative cell physiology to the cell cycle.

Key Papers

RtoA links initial cell type choice to the cell cycle in Dictyostelium.  Wood SA, Ammann RR, Brock DA, Li L, Spann T, Gomer RH.  Development 1996 122:3677-85
A protein containing a serine-rich domain with vesicle fusing properties mediates cell cycle-dependent cytosolic pH regulation.  Brazill DT, Caprette DR, Myler HA, Hatton RD, Ammann RR, Lindsey DF, Brock DA, Gomer RH.  J Biol Chem 2000 275:19231-40
The phase of the cell cycle at starvation influences the level of cellular Ca2+ and, thereby post-aggregative cell fate in Dictyostelium discoideum.  Azhar, M., Kennady, P.K., Pande, G., Espiritu, M., Holloman, W., Brazill, D., Gomer, R.H., and Nanjundiah, V.  Int. J. Dev. Bio. 2001 44, 405-414
Mutagenesis and gene identification in Dictyostelium by shotgun antisense.  Spann TP, Brock DA, Lindsey DF, Wood SA, Gomer RH.  Proc Natl Acad Sci U S A 1996 93:5003-7
Gene identification by shotgun antisense.  Gomer RH.  Methods 1999 18:311-5
 
 

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Last modified: October 02, 2003