Control of apoptosis by asymmetric cell division

Asymmetric cell division and apoptosis (programmed cell death) are two fundamental processes that are important for the development and function of multicellular organisms. We have found that the processes of asymmetric cell division and apoptosis can be functionally linked. Specifically, we show that asymmetric cell division in the nematode Caenorhabditis elegans is mediated by a pathway involving three genes, dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail, that directly control the enzymatic machinery responsible for apoptosis. Interestingly, the MIDA1-like protein GlsA of the alga Volvox carteri, as well as the Snail-related proteins Snail, Escargot, and Worniu of Drosophila melanogaster, have previously been implicated in asymmetric cell division. Therefore, C. elegans dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail may be components of a pathway involved in asymmetric cell division that is conserved throughout the plant and animal kingdoms. Furthermore, based on our results, we propose that this pathway directly controls the apoptotic fate in C. elegans, and possibly other animals as well.     

Plasma membrane-anchored chloroplasts are necessary for the gravisensing system of Ceratopteris richardii prothalli

Journal of Plant Research - The prothalli of the fern Ceratopteris richardii exhibit negative gravitropism when grown in darkness. However, no sedimentable organelles or substances have been...     

Negative phototropic response of rhizoid cells in the fern Adiantum capillus-veneris

In general, phototropic responses in land plants are induced by blue light and mediated by blue light receptor phototropins. In many cryptogam plants including the fern Adiantum capillus-veneris, however, red as well as blue light effectively induces a positive phototropic response in protonemal cells. In A. capillus-veneris, the red light effect on the tropistic response is mediated by phytochrome 3 (phy3), a chimeric photoreceptor of phytochrome and full-length phototropin. Here, we report red and blue light-induced negative phototropism in A. capillus-veneris rhizoid cells. Mutants deficient for phy3 lacked red light-induced negative phototropism, indicating that under red light, phy3 mediates negative phototropism in rhizoid cells, contrasting with its role in regulating positive phototropism in protonemal cells. Mutants for phy3 were also partially deficient in rhizoid blue light-induced negative phototropism, suggesting that phy3, in conjunction with phototropins, redundantly mediates the blue light response.     

Sperm cell architecture, insemination, and fertilization in the model fern, Ceratopteris richardii

Motile sperm cells of land plants are released directly into the environment and encounter numerous constraints on their way to the egg. Sperm cell organization, shape, size, and plasticity are crucial to the processes associated with fertilization. We conducted an ultrastructural investigation to detail insemination (sperm release, swimming and movement within the archegonium) and fertilization in the model fern Ceratopteris richardii. Gametophytes were grown from spores using sterile culture techniques and flooded in water when sexually mature. Materials were examined at different stages post-flooding. During insemination in C. richardii, the sperm cytoskeleton and flagella rearrange, and the coils of the cell extend while entering the neck canal. In this nearly linear configuration, the dense ridge, a densely compacted band of filaments presumed to be actin, expands to surround the leading edge of the sperm cell. This ridge fuses with the receptive site on the female gamete and is the sperm component that initiates contact with the egg nuclear envelope. All cellular components, except plastids, enter the egg cytoplasm. Sperm mitochondria are distinguishable from those of the egg because they are encased by two or three additional membranes and are sequestered from the zygote cytoplasm. During karyogamy, the sperm components, including the microtubule cytoskeleton (spline) and flagella, maintain their spatial integrity. Microtubules play key roles not only in sperm cell structure but also in facilitating karyogamy in this fern. After karyogamy is completed, microtubule arrays of the sperm cell and the components of the locomotory apparatus are disassembled. We provide the first demonstration of the likely involvement of sperm actin in egg penetration in land plants and new insights into the fate of paternal organelles. This study points to the roles sperm cell structure and dynamics play in the intricate processes of insemination and fertilization in land plants.     

Characterization and genetic analysis of antheridiogen-insensitive mutants in the fern Ceratopteris

WARNE, T. R., HICKOK, L. G. & SCOTT, R. S., 1988. Characterization and genetic analysis of antheridiogen-insensitive mutants in the fern Ceratopteris . The pheromone antheridiogen mediates the differentiation of male gametophytes in the fern Ceratopteris . Mutants insensitive to antheridiogen were isolated using an in vitro selection procedure. Antheridiogen-insensitive mutants exhibited partial or complete insensitivity to antheridiogen, but were normal in all other respects. Two mutants were completely insensitive to antheridiogen, whereas, another mutant was insensitive to supplemented antheridiogen, but produced male gametophytes in multispore cultures. Genetic analysis suggested a single gene basis for each mutant.     

Regulation of asymmetric cell division in the epidermis

For proper tissue morphogenesis, cell divisions and cell fate decisions must be tightly and coordinately regulated. One elegant way to accomplish this is to couple them with asymmetric cell divisions. Progenitor cells in the developing epidermis undergo both symmetric and asymmetric cell divisions to balance surface area growth with the generation of differentiated cell layers. Here we review the molecular machinery implicated in controlling asymmetric cell division. In addition, we discuss the ability of epidermal progenitors to choose between symmetric and asymmetric divisions and the key regulatory points that control this decision.     

Root hair development involves asymmetric cell division in Brachypodium distachyon and symmetric division in Oryza sativa

? The root epidermis of most angiosperms comprises hair (H) cells and nonhair (N) cells. H cells are shorter than N cells in grasses (Poaceae). ? The aim of this study was to determine the developmental basis for differences in H and N cell size in the grasses Brachypodium distachyon and Oryza sativa. ? We show that cytokinesis in the last cell division in each epidermal file is asymmetric in B. distachyon. The smaller daughter cell becomes an H cell and the larger cell forms an N cell. By contrast, asymmetric cytokinesis does not occur during H cell and N cell development in O. sativa and the differences in size arise because there is more cell expansion in N cells than in H cells after root hair initiation. ? The different sizes of mature H and N cells result from cell division asymmetry in B. distachyon but different rates of cell expansion in O. sativa. We hypothesize that the mechanism that includes asymmetric cytokinesis during the development of H and N cells evolved among the Pooideae or ancestors of this subfamily.     

Genetic map-based analysis of genome structure in the homosporous fern Ceratopteris richardii

Homosporous ferns have extremely high chromosome numbers relative to flowering plants, but the species with the lowest chromosome numbers show gene expression patterns typical of diploid organisms, suggesting that they may be diploidized ancient polyploids. To investigate the role of polyploidy in fern genome evolution, and to provide permanent genetic resources for this neglected group, we constructed a high-resolution genetic linkage map of the homosporous fern model species, Ceratopteris richardii (n = 39). Linkage map construction employed 488 doubled haploid lines (DHLs) that were genotyped for 368 RFLP, 358 AFLP, and 3 isozyme markers. Forty-one linkage groups were recovered, with average spacing between markers of 3.18 cM. Most loci (approximately 76%) are duplicated and most duplicates occur on different linkage groups, indicating that as in other eukaryotic genomes, gene duplication plays a prominent role in shaping the architecture of fern genomes. Although past polyploidization is a potential mechanism for the observed abundance of gene duplicates, a wide range in the number of gene duplicates as well as the absence of large syntenic regions consisting of duplicated gene copies implies that small-scale duplications may be the primary mode of gene duplication in C. richardii. Alternatively, evidence of past polyploidization(s) may be masked by extensive chromosomal rearrangements as well as smaller-scale duplications and deletions following polyploidization(s).     

Characterization of mutations that feminize gametophytes of the fern Ceratopteris.

Gametophytes of the fern Ceratopteris are either male or hermaphroditic. Their sex is epigenetically determined by the pheromone antheridiogen, which is secreted by the hermaphrodite and induces male and represses female development in other young, sexually undetermined gametophytes. To understand how antheridiogen represses the development of female traits at the genetic level, 16 new mutations that feminize the gametophyte in the presence of antheridiogen were identified and characterized. Seven are very tightly linked to the FEM1 locus previously described. Nine others define another locus named NOTCHLESS1 (NOT1), as several of the not1 mutants lack a meristem notch. Some not1 mutations also affect sporophyte development only when homozygous, indicating that the not1 mutations are recessive and that NOT1 is also required for normal sporophyte development. The epistatic interactions among FEM1, NOT1, and other sex-determining genes are described. This information was used to expand the genetic model of the sex-determining pathway in Ceratopteris. On the basis of this model, we can say that the presence of antheridiogen leads to the activation of the FEM1 gene, which not only promotes the differentiation of male traits, but also represses female development by activating the NOT1 gene. NOT1 represses the TRA genes necessary for the development of female traits in the gametophyte.     

Mechanisms of asymmetric stem cell division

Stem cells self-renew but also give rise to daughter cells that are committed to lineage-specific differentiation. To achieve this remarkable task, they can undergo an intrinsically asymmetric cell division whereby they segregate cell fate determinants into only one of the two daughter cells. Alternatively, they can orient their division plane so that only one of the two daughter cells maintains contact with the niche and stem cell identity. These distinct pathways have been elucidated mostly in Drosophila. Although the molecules involved are highly conserved in vertebrates, the way they act is tissue specific and sometimes very different from invertebrates.     

Snapping magnetosome chains by asymmetric cell division in magnetotactic bacteria

The mechanism by which prokaryotic cells organize and segregate their intracellular organelles during cell division has recently been the subject of substantial interest. Unlike other microorganisms, magnetotactic bacteria (MTB) form internal magnets (known as magnetosome chain) for magnetic orientation, and thus face an additional challenge of dividing and equipartitioning this magnetic receptor to their daughter cells. Although MTB have been investigated more than four decades, it is only recently that the basic mechanism of how MTB divide and segregate their magnetic organelles has been addressed. In this issue of Molecular Microbiology, the cell cycle of the model magnetotactic bacterium, Magnetospirillum gryphiswaldense is characterized by Katzmann and co-workers. The authors have found that M. gryphiswaldense undergoes an asymmetric cell division along two planes. A novel wedge-like type of cellular constriction is observed before separation of daughter cells and magnetosome chains, which is assumed to help cell cope with the magnetic force within the magnetosome chain. The data shows that the magnetosome chain becomes actively recruited to the cellular division site, in agreement with the previous suggestions described by Staniland et al. (2010), and the actin-like protein MamK is likely involved in this fast polar-to-midcell translocalization. With the use of cryo-electron tomography, an arc-shaped Z ring is observed near the division site, which is assumed to trigger the asymmetric septation of cell and magnetosome chain.     

Methylation of somatic and sperm DNA in the homosporous fern Ceratopteris richardii

Plants, in general, have a high proportion of their CpG and CpNpG nucleotide motifs modified with 5-methylcytosine (5mC). Developmental changes in the proportion of 5mC are evident in mammals, particularly during gametogenesis and embryogenesis, but little information is available from flowering plants due to the intimate association of gametes with sporophytic tissues. In ferns, sperm are uninucleate and free-swimming and thus are easily isolated. We have examined 5mC in DNA isolated from fern sperm and other tissues with methylation-sensitive and -insensitive restriction enzyme isoschizomers, Southern blots probed with chloroplast and nuclear ribosomal RNA genes and end-labeled restriction fragments. We conclude that fern sperm DNA is methylated to a similar or greater degree than DNA isolated from either sporophytes or gametophytes.     

Antheridogen activity in the fern Ceratopteris thalictroides (L.) Brongn.

Spores of the homosporous fern Ceratopteris thalictroides , in multispore culture, initially produce spatulate gametophytes bearing only antheridia (males) and cordate gametophytes bearing both antheridia and archegonia (hermaphrodites). When multispore cultures are sampled, the ratio of male to hermaphroditic gametophytes is a constant for each population examined. Four possible causes of such a sex ratio (cytoplasmic inheritance, nuclear inheritance, incipient heterospory and an antheridogen) are investigated. Evidence presented indicates that an antheridogen causes the existence of two gametophyte types, while one or more cytoplasmic units are the probable cause of the sex ratio. The activity of the antheridogen is to cause potentially hermaphroditic plants to become male. This activity was elucidated in monospore culture. Populational differences in antheridogen activity are also demonstrated. The significance of antheridogens is discussed in relation to the mating system of these plants.     

Lessons from development: A role for asymmetric stem cell division in cancer

Asymmetric stem cell division has emerged as a major regulatory mechanism for physiologic control of stem cell numbers. Reinvigoration of the cancer stem cell theory suggests that tumorigenesis may be regulated by maintaining the balance between asymmetric and symmetric cell division. Therefore, mutations affecting this balance could result in aberrant expansion of stem cells. Although a number of molecules have been implicated in regulation of asymmetric stem cell division, here, we highlight known tumor suppressors with established roles in this process. While a subset of these tumor suppressors were originally defined in developmental contexts, recent investigations reveal they are also lost or mutated in human cancers. Mutations in tumor suppressors involved in asymmetric stem cell division provide mechanisms by which cancer stem cells can hyperproliferate and offer an intriguing new focus for understanding cancer biology. Our discussion of this emerging research area derives insight from a frontier area of basic science and links these discoveries to human tumorigenesis. This highlights an important new focus for understanding the mechanism underlying expansion of cancer stem cells in driving tumorigenesis.     

Myosin-II puts the squeeze on asymmetric cell division

Asymmetric cell division--where two dissimilar daughter cells are produced--relies on asymmetric positioning of the telophase spindle midzone, which specifies the cleavage furrow. Ou et al. (2010) now report in Science a mechanism of asymmetric midzone positioning driven by a polarized cortical distribution of the contractile motor myosin-II.