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|New insight into the basis for differences in cell size
May 27, 2003 – When a cell divides, the two new cells are often differently sized. This
is seen in the cleavage of eggs in many species, as well as in the division of some stem cells,
which results in a pair of cells, one or both of which has a different, more highly specified,
character than its parent. A recent study has now shown one mechanism by which such cell size
asymmetry is achieved.
The Laboratory for Cell Asymmetry, under group director Fumio
Matsuzaki, has now identified a molecular determinant responsible for the generation of
unequally sized daughter cells during the division of neuroblasts in the fruitfly, Drosophila
melanogaster. This form of cell division generates a large neuroblast and a smaller ganglion
mother cell, or GMC. The neuroblast retains similar properties and potential to that of its
parent cell, while the GMC is more restricted in its developmental potency. Successive divisions
of neuroblasts and their progeny cells ultimately give rise to the Drosophila nervous system,
which provides a model for the fundamental processes at work in the development of more complex
neural networks, including the human nervous system.
Asymmetric cell division is an essential aspect of differentiation, the process in which daughter
cells acquire characteristics distinct from those of their parents. Previous studies have
identified a number of molecular factors that move selectively to one side of a dividing cell,
thereby determining the character, or fate, of both of the cells created in the division.
The factors that are currently know to act in asymmetric division have been shown to regulate
aspects such as the function and differentiative potential of the daughter cells, but the
question of how difference in cell size is regulated at the molecular level has remained unanswered.
The cellular mechanics of the process, however, have been studied, and it was known that different
types of cells divide into different sized progeny either by the off-center positioning of
the mitotic spindles (which dictate the point at which the cell cleaves), or their actual
physical asymmetry. In Drosophila neuroblasts, spindle asymmetry is the main factor in generating
unevenly sized cells.
In an article published in the May 27 issue of Current Biology, Naoyuki Fuse et al have shown
for the first time how the spindles are instructed to form asymmetrically. The process is
directed by one subunit of a G-protein (known as a heterotrimeric G protein) composed of three
distinct parts. G proteins generally function to bind the energy-carrying molecules GDP and
GTP, and activate or mediate a number of biological processes within the cell.
The Matsuzaki group found that in the absence of the Gβ subunit, neuroblasts form large,
symmetrical spindles as they prepare to divide and generate cells of nearly equal size, instead
of the normal large neuroblast/small GMC pair. Conversely, overexpression of Gβ resulted
in small spindles, suggesting that the subunit works to suppress spindle development. Interestingly,
this abnormal symmetry in size had no effect on the normal asymmetric distribution of other
fate-determining molecules, demonstrating that the mechanisms underlying fate and size asymmetry
are mutually independent. Flies with Gβ mutations also showed nervous system defects,
which suggests that cell size is in itself important to the function of neuroblasts.
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