RIKEN Review No. 41 (November, 2001): Focused on Bioarchitect Research
Asymmetric cell division: A basis for cellular diversity
Department of Developmental Neurobiology, Institute of Development,
Aging and Cancer, Tohoku University
Cell Asymmetry Group, RIKEN Center for Developmental Biology
Asymmetric cell division is a basic mechanism for generating cellular diversity and is utilized in a variety
of developmental contexts. Recent studies of Drosophila neural stem cells have revealed the roles
of asymmetric cell division in cell fate determination and have provided insights into the mechanism F. Matsuzaki
of asymmetric division. Our understanding now extends to the molecular nature of the cell polarity
underlying asymmetric division, which is conserved among neural stem cells, epithelial cells and fertilized
Asymmetric cell division
Animals develop from a single fertilized egg and are com-
prised of a functional multicellular organization consisting of
diverse cell types. How such cellular diversity is created is the
fundamental question in developmental biology. One major
mechanism for cells to take diﬀerent cell fates is asymmet-
ric division, which gives rise to two diﬀerent daughter cells
from a single progenitor cell.1) This type of division is used
to generate cellular diversity in various contexts of develop-
ment; a typical example is early egg cleavage that generates
blastomeres with diﬀerent fates by asymmetric division. The
stem cell system also relies on the asymmetric division to cre-
ate a population of identical or diverse cell types as observed
in neural development.
Fig. 1. Asymmetric division of Drosophila neuroblasts. Miranda
binds the transcription factor Prospero to localize it to the basal
Asymmetric segregation of cell fate determinants side of neuroblasts, and then this protein complex segregates into
the daughter cell, GMC. This process is essential for progeny neu-
In asymmetric division, the mother cell can generate two dis- rons to take their correct fates. On the apical side of neuroblasts,
cell polarity regulators such as Inscuteable localize.
tinct cells by transmitting cell fate determinants asymmetri-
cally into one daughter cell. This mechanism had long been
postulated from the early age of experimental embryology,
but it was not so long ago when asymmetrically segregated
determinants were experimentally shown. Findings of such
molecules came from studies on Drosophila neurogenesis,2, 3)
in which one could easily utilize genetic approaches such as
mutational screening. Drosophila neural stem cells, called
neuroblasts, divide asymmetrically into another neuroblast
and the ganglion mother cell (GMC) that is cleaved once
into a pair of neurons. In the mid 90s, neuronal fate determi-
nants, Numb (suppressor of Notch signaling) and Prospero
(transcription factor), were found to segregate to the sibling
GMC of neuroblasts during division (Fig. 1).4, 5) Since then,
Drosophila neuroblasts have been an excellent model system
to investigate key aspects of the asymmetric division as well
as of cell polarity. Subsequent studies have revealed that Fig. 2. Role of tumor suppressor proteins in neuroblasts: wild type
two important processes are associated with the asymmetric (left) and a mutant for a tumor suppressor gene dlg (right). Dlg
division of the neuroblast (Fig. 1):2, 3) ﬁrst, the asymmetric is essential for the localization of Miranda.
localization of neural fate determinants is achieved by spe-
ciﬁc adapter proteins such as Miranda that itself localizes to
the basal cell cortex.6, 7) More recently, a common upstream suppressor proteins, Giant larvae and Discs large.8, 9) The
mechanism was found to act in the localization of both Numb second critical mechanism is for the coordination of mitotic
and Prospero (Fig. 2), which includes two cortical tumor spindle orientation with the polarized localization of the de-
terminants (Fig. 1), which requires apical protein complexes neuronal fate determination during vertebrate neurogenesis.
including Inscuteable,10) Bazooka11, 12) and Pins.13) Recent
research suggests that neuroblasts, epithelial cells and nema-
tode fertilized eggs share the same molecular machinery that References
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be challenging to know how asymmetric division is involved in