Cell polarity and the mechanism of asymmetric cell division

During development one mechanism for generating different cell types is asymmetric cell division, by which a cell divides and contributes different factors to each of its daughter cells. Asymmetric cell division occurs through out the eukaryotic kingdom, from yeast to humans. Many asymmetric cell divisions occur in a defined orientation. This implies a cellular mechanism for sensing direction, which must ultimately lead to differences in gene expression between two daughter cells. In this review, we describe two classes of molecules: regulatory factors that are differentially expressed upon asymmetric cell division, and components of a signal transduction pathway that may define cell polarity. The lin-11 and mec-3 genes of C. elegans, the Isl-1 gene of mammals and the HO gene of yeast, encode regulatory factors that determine cell type of one daughter after asymmetric cell division. The CDC24 and CDC42 genes of yeast affect both bud positioning and orientation of mating projections, and thus may define a general cellular polarity. We speculate that molecules such as Cdc24 and Cdc42 may regulate expression of genes such as lin-11, mec-3, Isl-1 and HO upon asymmetric cell division.     

Cell growth and division in hypertonic medium

A comprehensive investigation has been made into the effects of raising medium strength on the growth and division of HeLa and other cell lines in tissue culture. Tonicity was raised by addition of concentrated solutions of NaCl, KCl, CaCl₂, choline chloride etc., and of substances such as urea, raffinose and glucose. It was established that osmotic effects were particularly important in arresting cells in metaphase, but some ions, e.g. K⁺ and Mg²⁺, more actively arrested metaphase than could be accounted for by osmotic effects alone. Some substances, particularly NaCl, allowed cells to progress into mitosis at concentrations which were adequate to prevent their exit from metaphase whereas other substances, such as MgCl₂, inhibited both entry into and exit from mitosis at about the same tonicity.Arrest of metaphases in hypertonic medium was not due to interference with the production of spindle but might have been attributable to excessive stickiness of the over-condensed chromosomes. Cells exposed to NaCl-supplemented medium exhibit a concentration dependent inhibition of macromolecular synthesis, protein synthesis being most affected, DNA synthesis less so and RNA synthesis least, except at slightly elevated tonicities which often produced a slight stimulation of the rate of synthetic activity.     

Cell division and cell growth in size

Summary and conclusion The coefficient of correlation between cell length and percentage mitosis in root-tips ofZea mays was found to be high and negative: r=–0·577±0·075. This value taken together with correlated data justifies the generality that cell division and cell size are inversely related. An analysis of the bases of the relation brings the conclusion that in an increasing cell population where growth in cell number and growth in cell size are taking place simultaneously, cell division is the independent and cell size the dependent variable. That is to say, other things being equal, the size of the cells is a result of the rate of cell multiplication. The explanation of this is given in the text.     

Studies in fission yeast on mechanisms of cell division site placement

One fundamental problem in cytokinesis is how the plane of cell division is established. In this review, we describe our studies on searching for "signals" that position the cell division plane, using fission yeast Schizosaccharomyces pombe. First, we take a genetic approach to determine how the nucleus may position the contractile ring in fission yeast. mid1p appears to link the position of the ring with the nuclear position, as it is required for proper placement of the contractile ring and is localized in a band at the cell surface overlying the nucleus. Second, we study how microtubules may function in the establishment of cell polarity at the cell tips. tea1p may be deposited on the cell surface by microtubules and function to recruit proteins involved in making actin structures. These studies suggest how microtubules may direct the assembly of the contractile ring in animal cells.     

Cell differentiation; Cell division, growth and death

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Cell Biology.     

Cell polarity and asymmetric division in the peripheral nervous system of Drosophila

During metazoan development, cell fate diversity is generated in part by asymmetric cell divisions, in which mother cells divide to produce two daughter cells with distinct developmental potentials. Adoption of different cell fates often relies on the polarised distribution and unequal segregation of cell-fate determinants. Unequal segregation of cell-fate determinants requires that the mother cell becomes polarised prior to mitosis. In response to this polarisation, cell-fate determinants localise asymmetrically and the mitotic spindle lines up with the pole to which cell-fate determinants accumulate, thereby leading to their unequal partitioning upon cytokinesis. I review here the regulatory mechanisms that establish cell asymmetry and orient this asymmetry relative to the body axis in the sensory organ lineages of Drosophila.     

Coupling of asymmetric division to polar placement of replication origin regions in Bacillus subtilis

Entry into sporulation in Bacillus subtilis is characterized by the formation of a polar septum, which asymmetrically divides the developing cell into forespore (the smaller cell) and mother cell compartments, and by migration of replication origin regions to extreme opposite poles of the cell. Here we show that polar septation is closely correlated with movement of replication origins to the extreme poles of the cell. Replication origin regions were visualized by the use of a cassette of tandem copies of lacO that had been inserted in the chromosome near the origin of replication and decorated with green fluorescent protein-LacI. The results showed that extreme polar placement of replication origin regions is not under sporulation control and occurred in stationary phase under conditions under which entry into sporulation was prevented. On the other hand, the formation of a polar septum, which is under sporulation control, was almost invariably associated with the presence of a replication origin region in the forespore. Moreover, cells in which the polar placement of origin regions was perturbed by deletion of the gene (smc) for the structural maintenance of chromosomes (SMC) protein were impaired in polar division. A small proportion ( approximately 1%) of the mutant cells were able to undergo asymmetric division, but the forespore compartment of these exceptional cells was generally observed to contain a replication origin region. Immunofluorescence microscopy experiments indicated that the block in polar division caused by the absence of SMC occurred at or prior to the step of bipolar Z-ring formation by the cell division protein FtsZ. A model is discussed in which polar division is under the dual control of sporulation and an event associated with the placement of a replication origin at the cell pole.     

Growth,cell division and sporulation in mycobacteria

Bacteria have the ability to adapt to different growth conditions and to survive in various environments. They have also the capacity to enter into dormant states and some bacteria form spores when exposed to stresses such as starvation and oxygen deprivation. Sporulation has been demonstrated in a number of different bacteria but Mycobacterium spp. have been considered to be non-sporulating bacteria. We recently provided evidence that Mycobacterium marinum and likely also Mycobacterium bovis bacillus Calmette–Guérin can form spores. Mycobacterial spores were detected in old cultures and our findings suggest that sporulation might be an adaptation of lifestyle for mycobacteria under stress. Here we will discuss our current understanding of growth, cell division, and sporulation in mycobacteria.     

Neurogenesis and asymmetric cell division

The astonishing cellular diversity in the central nervous system (CNS) arises from neural progenitors which can undergo different modes of symmetric and asymmetric divisions to self-renew as well as produce differentiated neuronal and glial progeny. Drosophila CNS neural progenitor cells, neuroblasts, have been utilised as a model to stimulate the understanding of the processes of asymmetric division, generation of neuronal lineages and, more recently, stem cell biology in vertebrates. Here we review some recent developments involving Drosophila and mammalian neural progenitor cells, highlighting some similarities and differences in the mechanisms that regulate their divisions during neurogenesis.     

Cell polarity and asymmetric cell division: the C. elegans early embryo

Cell polarity is crucial for many functions including cell migration, tissue organization and asymmetric cell division. In animal cells, cell polarity is controlled by the highly conserved PAR (PARtitioning defective) proteins. par genes have been identified in Caenorhabditis elegans in screens for maternal lethal mutations that disrupt cytoplasmic partitioning and asymmetric division. Although PAR proteins were identified more than 20 years ago, our understanding on how they regulate polarity and how they are regulated is still incomplete. In this chapter we review our knowledge of the processes of cell polarity establishment and maintenance, and asymmetric cell division in the early C. elegans embryo. We discuss recent findings that highlight new players in cell polarity and/or reveal the molecular details on how PAR proteins regulate polarity processes.     

Cell division genes promote asymmetric interaction between Numb and Notch in the Drosophila CNS.

Cell intrinsic and cell extrinsic factors mediate asymmetric cell divisions during neurogenesis in the Drosophila embryo. In the NB4-2->GMC-1->RP2/sib lineage, one of the well-studied neuronal lineages in the ventral nerve cord, the Notch (N) signaling interacts with the asymmetrically localized Numb (Nb) to specify sibling neuronal fates to daughter cells of GMC-1. In this current study, we have investigated asymmetric cell fate specifications by N and Nb in the context of cell cycle. We have used loss-of-function mutations in N and nb, cell division mutants cyclinA (cycA), regulator of cyclin A1 (rca1) and string/cdc25 phosphatase (stg), and the microtubule destabilizing agent, nocodazole, to investigate this issue. We report that the loss of cycA, rca1 or stg leads to a block in the division of GMC-1, however, this GMC-1 exclusively adopts an RP2 identity. While the loss of N leads to the specification of RP2 fates to both progeny of GMC-1 and loss of nb results in the specification of sib fates to these daughter cells, the GMC-1 in the double mutant between nb and cycA assumes a sib fate. These epistasis results indicate that both N and nb function downstream of cell division genes and that progression through cell cycle is required for the asymmetric localization of Nb. In the absence of entry to metaphase, the Nb protein prevents the N signaling from specifying sib fate to the RP2/sib precursor. These results are also consistent with our finding that the sib cell is specified as RP2 in N; nb double mutants. Finally, our results show that nocodazole-arrested GMC-1 in wild-type embryos randomly assumes either an RP2 fate or a sib fate. This suggests that microtubules are involved in mediating the antagonistic interaction between Nb and N during RP2 and sib fate specification.     

Cell growth and cell division in the rod-shaped actinomycete Corynebacterium glutamicum

Bacterial cell growth and cell division are highly complicated and diversified biological processes. In most rod-shaped bacteria, actin-like MreB homologues produce helicoidal structures along the cell that support elongation of the lateral cell wall. An exception to this rule is peptidoglycan synthesis in the rod-shaped actinomycete Corynebacterium glutamicum, which is MreB-independent. Instead, during cell elongation this bacterium synthesizes new cell-wall material at the cell poles whereas the lateral wall remains inert. Thus, the strategy employed by C. glutamicum to acquire a rod-shaped morphology is completely different from that of Escherichia coli or Bacillus subtilis. Cell division in C. glutamicum also differs profoundly by the apparent absence in its genome of homologues of spatial or temporal regulators of cell division, and its cell division apparatus seems to be simpler than those of other bacteria. Here we review recent advances in our knowledge of the C. glutamicum cell cycle in order to further understand this very different model of rod-shape acquisition.