Wnt signaling controls the stem cell-like asymmetric division of the epithelial seam cells during C. elegans larval development

Metazoan stem cells repopulate tissues during adult life by dividing asymmetrically to generate another stem cell and a cell that terminally differentiates. Wnt signaling regulates the division pattern of stem cells in flies and vertebrates. While the short-lived nematode C. elegans has no adult somatic stem cells, the lateral epithelial seam cells divide in a stem cell-like manner in each larval stage, usually generating a posterior daughter that retains the seam cell fate and an anterior daughter that terminally differentiates. We show that while wild-type adult animals have 16 seam cells per side, animals with reduced function of the TCF homolog POP-1 have as many as 67 seam cells, and animals with reduced function of the β-catenins SYS-1 and WRM-1 have as few as three. Analysis of seam cell division patterns showed alterations in their stem cell-like divisions in the L2-L4 stages: reduced Wnt signaling caused both daughters to adopt non-seam fates, while activated Wnt signaling caused both daughters to adopt the seam fate. Therefore, our results indicate that Wnt signaling globally regulates the asymmetric, stem cell-like division of most or all somatic seam cells during C. elegans larval development, and that Wnt pathway regulation of stem cell-like behavior is conserved in nematodes.     

Symmetry Breaking in Plants: Molecular Mechanisms Regulating Asymmetric Cell Divisions in Arabidopsis

Asymmetric cell division generates cell types with different specialized functions or fates. This type of division is critical to the overall cellular organization and development of many multicellular organisms. In plants, regulated asymmetric cell divisions are of particular importance because cell migration does not occur. The influence of extrinsic cues on asymmetric cell division in plants is well documented. Recently, candidate intrinsic factors have been identified and links between intrinsic and extrinsic components are beginning to be elucidated. A novel mechanism in breaking symmetry was revealed that involves the movement of typically intrinsic factors between plant cells. As we learn more about the regulation of asymmetric cell divisions in plants, we can begin to reflect on the similarities and differences between the strategies used by plants and animals. Focusing on the underlying molecular mechanisms, this article describes three selected cases of symmetry-breaking events in the model plant Arabidopsis thaliana. These examples occur in early embryogenesis, stomatal development, and ground tissue formation in the root.Plant cells are surrounded by rigid cell walls that prevent cell movement. Precisely oriented cell division is especially important in the absence of cell migration. When a plant cell divides, a new wall forms between the daughter cells; this permanently delineates their relative positions. As a consequence, the selection of the division plane is crucial for plant tissue organization and overall organ architecture.The selection of the division plane is unique in plants compared with other organisms (for a detailed review of plant cytokinesis see Jürgens 2005). In budding yeast, landmarks at previous bud-sites position the division plane (see Slaughter et al. 2009), whereas in fission yeast it is positioned by the nucleus. The position of the centrosomes and the mitotic spindle determine division plane orientation in animal cells (Balasubramanian et al. 2004; see Munro and Bowerman 2009). In plants, the division plane is positioned by a ring of microtubules and F-actin, called the preprophase band that forms at the cell periphery (Mineyuki 1999). Despite these striking differences, similarities are beginning to emerge. For example, in budding yeast and animals, GTPase activation plays an important role in positioning division planes (Balasubramanian et al. 2004; see McCaffrey and Macara 2009; Slaughter et al. 2009; Munro and Bowerman 2009; Prehoda 2009). In plants, a GTPase was recently found to be localized at the preprophase band and may provide spatial information during division (Xu et al. 2008). Therefore, common molecular mechanisms may underlie division plane selection in plants and animals.In all organisms, asymmetric cell division is a common method to obtain distinct cell types from a single progenitor cell. Before an asymmetric division a cell must first establish an internal asymmetry; this process is termed breaking symmetry. Breaking symmetry can be generally defined as the asymmetric organization of cellular components along one axis leading to cellular polarization as a prerequisite to division. An asymmetric cell division can generate two cells of different morphology (i.e., size and/or shape) or different specialized functions or fates. Specifically, the products of asymmetric cell divisions fall into two major categories. In one case, a mother cell can divide asymmetrically to produce a daughter cell to replace it and a daughter cell with a distinct fate, as in the case of stem cell divisions. Alternatively, a mother cell can divide asymmetrically to produce two distinct daughter cells at the expense of mother cell identity. Following division, there are two basic mechanisms by which a mother cell generates daughters that are distinct from itself. One mechanism is intrinsic to the cell and is defined by segregation of cellular determinants before division. The other mechanism is extrinsic to the cell and is defined by external cues that direct daughter cell fate (Horvitz and Herskowitz 1992). Intrinsic and extrinsic mechanisms are not necessarily independent and often work in combination to direct asymmetric division and specification of daughter cells.The first zygotic division of fucoid brown algae, such as Fucus, is one of the earliest studied examples of symmetry breaking in plants regulated by both extrinsic and intrinsic mechanisms. Fucus zygotes are an excellent organism in which to examine the cellular biology underlying asymmetric cell division (for a recent review see Homble and Leonetti 2007). In the presence of extrinsic cues, such as light, the asymmetric zygotic division is oriented perpendicular to the light gradient so that one cell resides on the “shady” side of the gradient (Kropf 1992, 1997; Alessa and Kropf 1999). In the absence of environmental cues, the division is oriented relative to the sperm entry site and therefore appears random within a field of cells (Hable and Kropf 2000). This indicates that Fucus zygotes have an intrinsic mechanism to break symmetry in the absence of extrinsic cues. This intrinsic mechanism occurs rapidly after fertilization, however it can later be overridden by extrinsic cues. Although much is known about the role of the cytoskeleton, membrane depolarization, and ion flux in Fucus embryo polarization, the molecular components regulating these events remain unknown because of a lack of molecular tools. To address the molecular mechanisms regulating asymmetric cell divisions in plants, the use of a more genetically tractable plant is necessary.In the model plant Arabidopsis thaliana, many genes that are involved in asymmetric cell division have been identified. Interestingly, many of these genes are thought to function in both asymmetric division and subsequent cell fate specification suggesting that, in plants, these processes are tightly linked. Despite these advances, relatively little is known about the cellular processes of breaking symmetry in plants. Because of these two caveats, the term breaking symmetry must be defined more generally in plants. We use this term to describe a process in which a cell divides asymmetrically to form a daughter cell with a distinct fate. Here we discuss three examples in which the molecular mechanisms that participate in symmetry-breaking events in plants are beginning to be elucidated. These examples occur in early embryogenesis, formation of stomata, and root development (Fig. 1). We confine the topics of this article to Arabidopsis thaliana because the majority of the experimental work, particularly using molecular genetics, is focused on this species.Open in a separate windowFigure 1.An Arabidopsis plant. Schematic of an adult plant depicting roots, leaves, stems, and flowers. In this article, three symmetry-breaking events are discussed. These examples are taken from different organs of the plant. The first example is taken from embryo development, which occurs after fertilization of the flower in the silique (seed pod) in Arabidopsis. Next, symmetry breaking in the leaf epidermis during stomatal development is discussed. Finally, the asymmetric cell division that gives rise to the ground tissue in the root is considered.     

Drosophila neural progenitor polarity and asymmetric division

In the Drosophila embryonic central nervous system, the neural precursor cells called neuroblasts undergo a number of asymmetric divisions along the apical-basal axis to give rise to different daughter cells of distinct fates. This review summarizes recent progress in understanding the mechanisms of these asymmetric cell divisions. We discuss proteins that are localized at distinct domains of cortex in the neuroblasts and their role in generating asymmetry. We also review uniformly cortical localized factors and actin cytoskeleton-associated motor proteins with regard to their potential role to serve as a link between distinct cortical domains in the neuroblasts. In this review, asymmetric divisions of sensory organ precursor and larval neuroblasts are also briefly discussed.     

Roles for polarity and nuclear determinants in specifying daughter cell fates after an asymmetric cell division in the maize leaf

Asymmetric cell divisions occur repeatedly during plant development, but the mechanisms by which daughter cells are directed to adopt different fates are not well understood [1,2]. Previous studies have demonstrated roles for positional information in specification of daughter cell fates following asymmetric divisions in the embryo [3] and root [4]. Unequally inherited cytoplasmic determinants have also been proposed to specify daughter cell fates after some asymmetric cell divisions in plants [1,2,5], but direct evidence is lacking. Here we investigate the requirements for specification of stomatal subsidiary cell fate in the maize leaf by analyzing four mutants disrupting the asymmetric divisions of subsidiary mother cells (SMCs). We show that subsidiary cell fate does not depend on proper localization of the new cell wall during the SMC division, and is not specified by positional information acting on daughter cells after completion of the division. Instead, our data suggest that specification of subsidiary cell fate depends on polarization of SMCs and on inheritance of the appropriate daughter nucleus. We thus provide evidence of a role for unequal inheritance of an intracellular determinant in specification of cell fate after an asymmetric plant cell division.     

Comparative analysis of embryonic cell lineage between Caenorhabditis briggsae and Caenorhabditis elegans

Comparative genomic analysis of important signaling pathways in Caenorhabditis briggsae and Caenorhabditis elegans reveals both conserved features and also differences. To build a framework to address the significance of these features we determined the C. briggsae embryonic cell lineage, using the tools StarryNite and AceTree. We traced both cell divisions and cell positions for all cells through all but the last round of cell division and for selected cells through the final round. We found the lineage to be remarkably similar to that of C. elegans. Not only did the founder cells give rise to similar numbers of progeny, the relative cell division timing and positions were largely maintained. These lineage similarities appear to give rise to similar cell fates as judged both by the positions of lineally equivalent cells and by the patterns of cell deaths in both species. However, some reproducible differences were seen, e.g., the P4 cell cycle length is more than 40% longer in C. briggsae than that in C. elegans (p < 0.01). The extensive conservation of embryonic development between such divergent species suggests that substantial evolutionary distance between these two species has not altered these early developmental cellular events, although the developmental defects of transpecies hybrids suggest that the details of the underlying molecular pathways have diverged sufficiently so as to not be interchangeable.     

Cell–cell communication in Arabidopsis early embryogenesis

The basic body plan of the adult plant is established during embryogenesis, resulting in the juvenile form of the seedling. Arabidopsis embryogenesis is distinguished by a highly regular pattern of cell divisions. Some of these divisions are asymmetric, generating daughter cells with different fates. However, their subsequent differentiation might still depend on cell–cell communication to be fully accomplished or maintained. In some cases, cell fate specification solely depends on cell–cell communication that in general plays an important role in the generation of positional information within the embryo. Although auxin-dependent signalling has received much attention, other ways of cell–cell communication have also been demonstrated or suggested. This review focuses on aspects of pattern formation and cell–cell communication during Arabidopsis embryogenesis up to the mid-globular stage of development.     

Ephrin-Eph signalling drives the asymmetric division of notochord/neural precursors in Ciona embryos

Asymmetric cell divisions produce two sibling cells with distinct fates, providing an important means of generating cell diversity in developing embryos. Many examples of such cell divisions have been described, but so far only a limited number of the underlying mechanisms have been elucidated. Here, we have uncovered a novel mechanism controlling an asymmetric cell division in the ascidian embryo. This division produces one notochord and one neural precursor. Differential activation of extracellular-signal-regulated kinase (ERK) between the sibling cells determines their distinct fates, with ERK activation promoting notochord fate. We first demonstrate that the segregation of notochord and neural fates is an autonomous property of the mother cell and that the mother cell acquires this functional polarity via interactions with neighbouring ectoderm precursors. We show that these cellular interactions are mediated by the ephrin-Eph signalling system, previously implicated in controlling cell movement and adhesion. Disruption of contacts with the signalling cells or inhibition of the ephrin-Eph signal results in the symmetric division of the mother cell, generating two notochord precursors. Finally, we demonstrate that the ephrin-Eph signal acts via attenuation of ERK activation in the neural-fated daughter cell. We propose a model whereby directional ephrin-Eph signals functionally polarise the notochord/neural mother cell, leading to asymmetric modulation of the FGF-Ras-ERK pathway between the daughter cells and, thus, to their differential fate specification.     

Segregation of germ layer fates by nuclear migration-dependent localization of Not mRNA

An important step in early embryonic development is the allocation and segregation of germ layer fates into distinct embryonic regions. However, the mechanism that segregates the mesendoderm into mesoderm and endoderm fates remains largely unknown in most animals. Here, using ascidians, a primitive chordate, we show that these fates are segregated by partitioning of asymmetrically localized Not mRNA from the mesendoderm cell to its mesodermal daughter. Migration of the mesendoderm cell nucleus to the future mesoderm-forming region, release of Not mRNA from the nucleus, Wnt5α-dependent local retention of the mRNA, and subsequent repositioning of the mitotic spindle to the center of the cell are each required for the asymmetric localization and partitioning of Not mRNA. Our results show that nuclear migration plays an unexpected role in asymmetric cell divisions that segregate germ layer fates in chordate embryos.     

Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts

Stem cells and neuroblasts derived from mouse embryos undergo repeated asymmetric cell divisions, generating neural lineage trees similar to those of invertebrates. In Drosophila, unequal distribution of Numb protein during mitosis produces asymmetric cell divisions and consequently diverse neural cell fates. We investigated whether a mouse homologue m-numb had a similar role during mouse cortical development. Progenitor cells isolated from the embryonic mouse cortex were followed as they underwent their next cell division in vitro. Numb distribution was predominantly asymmetric during asymmetric cell divisions yielding a beta-tubulin III(-) progenitor and a beta-tubulin III(+) neuronal cell (P/N divisions) and predominantly symmetric during divisions producing two neurons (N/N divisions). Cells from the numb knockout mouse underwent significantly fewer asymmetric P/N divisions compared to wild type, indicating a causal role for Numb. When progenitor cells derived from early (E10) cortex undergo P/N divisions, both daughters express the progenitor marker Nestin, indicating their immature state, and Numb segregates into the P or N daughter with similar frequency. In contrast, when progenitor cells derived from later E13 cortex (during active neurogenesis in vivo) undergo P/N divisions they produce a Nestin(+) progenitor and a Nestin(-) neuronal daughter, and Numb segregates preferentially into the neuronal daughter. Thus during mouse cortical neurogenesis, as in Drosophila neurogenesis, asymmetric segregation of Numb could inhibit Notch activity in one daughter to induce neuronal differentiation. At terminal divisions generating two neurons, Numb was symmetrically distributed in approximately 80% of pairs and asymmetrically in 20%. We found a significant association between Numb distribution and morphology: most sisters of neuron pairs with symmetric Numb were similar and most with asymmetric Numb were different. Developing cortical neurons with Numb had longer processes than those without. Numb is expressed by neuroblasts and stem cells and can be asymmetrically segregated by both. These data indicate Numb has an important role in generating asymmetric cell divisions and diverse cell fates during mouse cortical development.     

CWN-1 functions with DSH-2 to regulate C. elegans asymmetric neuroblast division in a β-catenin independent Wnt pathway

In Caenorhabditis elegans, Wnt signaling regulates many asymmetric cell divisions. During embryogenesis, the C. elegans Dishevelled (Dsh) homolog, DSH-2, regulates asymmetric neuroblast division of the ABpl/rpppa blast cell. Dsh is a key intracellular component of both β-catenin dependent and β-catenin independent Wnt pathways. In C. elegans, most of the well-characterized asymmetric cell divisions regulated by Wnts are dependent on β-catenin. In the ABpl/rpppa neuroblast division, however, we determined that DSH-2 regulates cell polarity through a β-catenin independent Wnt pathway. We also established that the C. elegans Wnt homolog, cwn-1, functions to regulate asymmetric division of the ABpl/rpppa blast cell. Our results indicated that cwn-1 does not act alone in this process, and it functions with another redundant ligand that appears not to be a Wnt. Finally, we show widespread requirements for DSH-2 during embryogenesis in the generation of many other neurons. In particular, DSH-2 function is necessary for the correct production of the embryonic ventral cord motor neurons. This study demonstrates a role for DSH-2 and Wnt signaling in neuronal specification during C. elegans embryogenesis.     

Polarization of Drosophila Neuroblasts During Asymmetric Division

During Drosophila development, neuroblasts divide to generate progeny with two different fates. One daughter cell self-renews to maintain the neuroblast pool, whereas the other differentiates to populate the central nervous system. The difference in fate arises from the asymmetric distribution of proteins that specify either self-renewal or differentiation, which is brought about by their polarization into separate apical and basal cortical domains during mitosis. Neuroblast symmetry breaking is regulated by numerous proteins, many of which have only recently been discovered. The atypical protein kinase C (aPKC) is a broad regulator of polarity that localizes to the neuroblast apical cortical region and directs the polarization of the basal domain. Recent work suggests that polarity can be explained in large part by the mechanisms that restrict aPKC activity to the apical domain and those that couple asymmetric aPKC activity to the polarization of downstream factors. Polarized aPKC activity is created by a network of regulatory molecules, including Bazooka/Par-3, Cdc42, and the tumor suppressor Lgl, which represses basal recruitment. Direct phosphorylation by aPKC leads to cortical release of basal domain factors, preventing them from occupying the apical domain. In this framework, neuroblast polarity arises from a complex system that orchestrates robust aPKC polarity, which in turn polarizes substrates by coupling phosphorylation to cortical release.Cells use polarity for remarkably diverse functions. In this article, I discuss a polarity that is harnessed to generate daughter cells with different fates. Using polarity to divide asymmetrically addresses several challenges that complex organisms face. The diversification of cell types and tissues that occurs during the development of complex organisms is one such challenge. Drosophila neuroblasts, the subject of this article, undergo repeated symmetry breaking asymmetric cell divisions (ACDs) to populate the central nervous system. In a similar manner in adult organisms, ACDs are important for adult homeostasis, replenishing cells that are turned over during the course of normal physiology (Betschinger and Knoblich 2004).A fundamental aspect of ACD is the production of daughter cells containing distinct fate determinants. To segregate fate determinants, the cell becomes polarized to form mutually exclusive cortical domains, each with a set of fate determinants appropriate for one of the two daughter cells. The cleavage furrow forms at the interface of the two domains, partitioning the fate determinants into the two daughter cells where they function to either self-renew (to keep the progenitor population) or to differentiate (e.g., by changing the pattern of gene expression). One of the unique features of the symmetry breaking that occurs during ACD, at least as implemented by the neuroblast, is that it is remarkably dynamic, developing early in mitosis and depolarizing following the completion of cytokinesis.Since the discovery of the first polarized components, neuroblasts have been an excellent model system for investigating the mechanisms of cell polarization and have been extensively analyzed. Although aspects of neuroblast polarity remain unclear, a core framework for how polarity is created and maintained is emerging. In this article, I focus on neuroblast polarity as centered around the activity of atypical protein kinase C, which has emerged as a key regulator of the process. In this framework, neuroblast polarity can be explained by events that polarize aPKC and those that couple aPKC activity to the polarization of fate determinants.     

Nematode Postembryonic Cell Lineages

The complete postembryonic ceil lineages of the free-living nentatodes Caenorhabditis elegans and Panagrellus redivivus are known. Postembryonic cell divisions lead to substantial increases in the number of cells and, in most cases, in the number of types of cells in the neuronal, muscular, hypodermal, and digestive systems. The patterns of postembyronic cell divisions are essentially invariant and generate a fixed number of progeny cells of strictly specified fates. Cell fates depend upon both lineage history and cell-cell interactions: lineage limits the developmental potential of each cell and, for certain cells, cell-cell interactions specify which of a small number of alternative potential fates is acquired. Relatively simple differences in cell lineage account for some of the striking differences in gross morphology both between sexes and between species. Genetic studies indicate that these cell lineage differences reflect one or a few relatively simple mutational events. Interspecific differences in cell lineage are likely to be good indicators of evolutionary distance and may be helpful in defining taxonomic relationships. Both the techniques utilized in, and the information acquired from, studies of cell lineages in C. elegans and P. redivivus may prove useful to other hematologists.     

Timing cell-fate determination during asymmetric cell divisions

From invertebrates to mammals, cell-cycle progression during an asymmetric cell division is accompanied by precisely timed redistribution of cell-fate determinants so that they segregate asymmetrically to enable the two daughter cells to choose different fates. Interestingly, studies on how cell fates are specified in such divisions reveal that the same fate determinants can be reiteratively used to specify a variety of cell types through multiple rounds of cell divisions or to exert seemingly contradictory effects on cell proliferation and differentiation. Here I summarize the molecular mechanisms governing asymmetric cell division and review recent findings pointing to a novel mechanism for coupling intracellular signaling and cell-cycle progression. This mechanism uses changes in the morphology, subcellular distribution, and molecular composition of cellular organelles like the Golgi apparatus and centrosomes, which not only accompany the progression of cell cycle to activate but also temporally constrain the activity of fate determinants during asymmetric cell divisions.     

Drosophila Anillin is unequally required during asymmetric cell divisions of the PNS

During Drosophila embryogenesis, timely and orderly asymmetric cell divisions ensure the correct number of each cell type that make up the sensory organs of the larval PNS. We report a role of scraps, Drosophila Anillin, during these divisions. Anillin, a constitutive member of the contractile ring is essential for cytokinesis in Drosophila and vertebrates. During embryogenesis we find that zygotically transcribed scraps is required specifically for the unequal cell divisions, those in which cytokinesis occurs in an “off-centred” manner, of the pIIb and pIIIb neuronal precursor cells, but not the equal cell divisions of the lineage related precursor cells. Complementation and genetic rescue studies demonstrate this effect results from zygotic scraps and leads to polyploidy, ectopic mitosis, and loss of the neuronal precursor daughter cells. The net result of which is the formation of incomplete sense organs and embryonic lethality.     

Wnt signaling and a Hox protein cooperatively regulate psa-3/Meis to determine daughter cell fate after asymmetric cell division in C. elegans

Asymmetric cell division is a mechanism for achieving cellular diversity. In C. elegans, many asymmetric cell divisions are controlled by the Wnt-MAPK pathway through POP-1/TCF. It is poorly understood, however, how POP-1 determines the specific fates of daughter cells. We found that nob-1/Hox, ceh-20/Pbx, and a Meis-related gene, psa-3, are required for asymmetric division of the T hypodermal cell. psa-3 expression was asymmetric between the T cell daughters, and it was regulated by POP-1 through a POP-1 binding site in the psa-3 gene. psa-3 expression was also regulated by NOB-1 and CEH-20 through a NOB-1 binding sequence in a psa-3 intron. PSA-3 can bind CEH-20 and function after the T cell division to promote the proper fate of the daughter cell. These results indicate that cooperation between Wnt signaling and a Hox protein functions to determine the specific fate of a daughter cell.     

MEL-47, a novel protein required for early cell divisions in the nematode <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

In the early Caenorhabditis elegans embryo, a rapid succession of cell divisions, many of them asymmetric, form blastomeres that differ in size, cell cycle duration and developmental potential. These early cell cycles are highly regulated and controlled by maternally contributed products. We describe here a novel gene, mel-47, that is required maternally for the proper execution of the early cell cycles. mel-47(yt2) mutants arrest as completely disorganized embryos with 50–80 cells of variable size. The earliest defects we found are changes in the absolute and relative duration of the very early embryonic cell cycles. In particular, the posterior cell of the two-cell embryo divides late compared with its anterior sister. Frequently the daughter cells remain connected through chromatin bridges after the early cleavage divisions indicating that the chromosomes do not segregate properly. The cell cycle delay can be suppressed by knocking down a DNA replication check point. Therefore we propose that mel-47 is required for proper DNA replication in the early embryo. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Postembryonic nongonadal cell lineages of the nematode Panagrellus redivivus: Description and comparison with those of Caenorhabditis elegans

The postembryonic nongonadal cell lineages of the nematode Panagrellus redivivus are described and compared with those of Caenorhabditis elegans. The newly hatched larvae of P. redivivus females and males and C. elegans hermaphrodites and males are very similar. An almost identical set of blast cells divides postembryonically in P. redivivus and C. elegans to produce similar changes in the neuronal, muscular, hypodermal, and digestive systems. Most of these cell lineages are invariant; however, there is substantial variability in the number of cell divisions in the relatively extensive lineages of the lateral hypodermis of P. redivivus. Typically, in P. redivivus females, 55 blast cells generate 635 surviving progeny and 29 cell deaths; in P. redivivus males, 59 blast cells generate 758 surviving progeny and 35 cell deaths. The lineages generating the cells of the male tails of P. redivivus and C. elegans are almost identical; thus, the grossly different characteristics of these structures must reflect differences in the morphogenesis of cells equivalent in lineage history. Laser ablation experiments demonstrate that the gonad induces vulva development and that cell-cell interactions are important in specifying the fates of hypodermal precursor cells. The lateral hypodermal lineages provide striking examples of the apparent construction of complex lineages from modular sublineages; one simple pattern of cell divisions and cell fates occurs 70 times in the P. redivivus female. The differences in cell lineage between P. redivivus and C. elegans are relatively minor, and many appear to have involved two types of evolutionary change: the replacement of sublineages, and the modification of sublineages by the four classes of lineage transformations previously proposed based on a comparison of P. redivivus and C. elegans gonadal cell lineages (Sternberg and Horvitz, 1981). These types of differences suggest that the genetic programming of cell lineage includes instructions specifying where and when a particular sublineage is utilized, and other instructions specifying the nature of that sublineage.     

C.elegans野生型和par突变体早期胚胎卵裂的观察

不对称分裂在动植物的发育中起到了非常重要的作用。Caenorhabditis elegans（C．elegans）胚胎最早的两次卵裂为研究控制不对称分裂的机制提供了很好的机会。用普通光学显微镜观察了野生型胚胎早期卵裂和par-1、par-2、par-3、par-4突变体胚胎的早期卵裂。野生型胚胎最早的分裂是不等的,产生了两个不同大小的子细胞。两个子细胞又以不同的方向进行第二次分裂。在C．elegans中任意一个par基因的缺失会使胚胎的第一次卵裂丧失不对称性。这会导致一些发育调控因子不能在特定的胚胎细胞中准确地定位,造成细胞分裂纺锤体方向的异常。par类基因参与不对称性的建立,这种不对称性决定了C．elegans身体的前后轴。     

Specification of polarity of teloblastogenesis in the oligochaete annelid Tubifex: cellular basis for bilateral symmetry in the ectoderm

Ectodermal teloblastogenesis in the oligochaete annelid Tubifex is a spatiotemporally regulated process that gives rise to four bilateral pairs of ectoteloblasts (N, O, P, and Q) that assume distinct fates. Ectoteloblasts on either side of the embryo arise from an invariable sequence of asymmetric cell divisions of a proteloblast, NOPQ, which occur with a defined orientation with respect to the embryonic axes: the N teloblast is generated first and located ventralmost, and the Q teloblast, which is generated next, is located dorsalmost; finally, the O and P teloblasts are generated by almost equal division of their precursor cell, OP. Polarity of teloblastogenesis on one side of the embryo is a mirror image of the other; this mirror symmetry of ectoteloblasts about the embryo's midline gives rise to the bilaterally symmetric organization of the ectoderm. In this study, we examined whether cellular interactions are involved in specification of polarity of asymmetric cell divisions in NOPQ cells. A set of cell transplantation experiments demonstrated that NOPQ cells are initially uncommitted in terms of division pattern and cell fates: If a left NOPQ cell is transplanted to the right side of a host embryo, it exhibits a polarity comparable to that of right NOPQ cells. The results of another set of cell transplantation experiments suggest that contact between NOPQ cells serves as an external cue for their polarization, irrespective of their position in the embryo, and that in the absence of host NOPQ cells, transplanted NOPQ cells can be polarized according to positional information residing in the host embryo. The competence of NOPQ cells to respond to external cues tapers down before their division into N and OPQ. A set of cell ablation experiments demonstrated that neighboring cells such as posteriorly located M teloblasts and anterolaterally located micromeres play a role in controlling spatial aspects of NOPQ's behavior that gives rise to their division along the dorsoventral axis. These results suggest that NOPQ cells, which do not initially have a rigidly fixed polarity, become polarized through external cues. Possible sources of signals for this polarizing induction are discussed in the light of the present results.