Dynamics of Cell Packing and Polar Order in Developing Epithelia

During development, organs with different shape and functionality form from a single fertilized egg cell. Mechanisms that control shape, size and morphology of tissues pose challenges for developmental biology. These mechanisms are tightly controlled by an underlying signaling system by which cells communicate to each other. However, these signaling networks can affect tissue size and morphology through limited processes such as cell proliferation, cell death and cell shape changes,which are controlled by cell mechanics and cell adhesion. One example of such a signaling system is the network of interacting proteins that control planar polarization of cells. These proteins distribute asymmetrically within cells and their distribution in each cell determines of the polarity of the neighboring cells. These proteins control the pattern of hairs in the adult Drosophila wing as well as hexagonal repacking of wing cells during development. Planar polarity proteins also control developmental processes such as convergent-extension. We present a theoretical study of cell packing geometry in developing epithelia. We use a vertex model to describe the packing geometry of tissues, for which forces are balanced throughout the tissue. We introduce a cell division algorithm and show that repeated cell division results in the formation of a distinct pattern of cells, which is controlled by cell mechanics and cell-cell interactions. We compare the vertex model with experimental measurements in the wing disc of Drosophila and quantify for the first time cell adhesion and perimeter contractility of cells. We also present a simple model for the dynamics of polarity order in tissues. We identify a basic mechanism by which long-range polarity order throughout the tissue can be established. In particular we study the role of shear deformations on polarity pattern and show that the polarity of the tissue reorients during shear flow. Our simple mechanisms for ordering can account for the processes observed during development of the Drosophila wing

Dynamics of Cell Packing and Polar Order in Developing Epithelia

During development, organs with different shape and functionality form from a single fertilized egg cell. Mechanisms that control shape, size and morphology of tissues pose challenges for developmental biology. These mechanisms are tightly controlled by an underlying signaling system by which cells communicate to each other. However, these signaling networks can affect tissue size and morphology through limited processes such as cell proliferation, cell death and cell shape changes,which are controlled by cell mechanics and cell adhesion. One example of such a signaling system is the network of interacting proteins that control planar polarization of cells. These proteins distribute asymmetrically within cells and their distribution in each cell determines of the polarity of the neighboring cells. These proteins control the pattern of hairs in the adult Drosophila wing as well as hexagonal repacking of wing cells during development. Planar polarity proteins also control developmental processes such as convergent-extension. We present a theoretical study of cell packing geometry in developing epithelia. We use a vertex model to describe the packing geometry of tissues, for which forces are balanced throughout the tissue. We introduce a cell division algorithm and show that repeated cell division results in the formation of a distinct pattern of cells, which is controlled by cell mechanics and cell-cell interactions. We compare the vertex model with experimental measurements in the wing disc of Drosophila and quantify for the first time cell adhesion and perimeter contractility of cells. We also present a simple model for the dynamics of polarity order in tissues. We identify a basic mechanism by which long-range polarity order throughout the tissue can be established. In particular we study the role of shear deformations on polarity pattern and show that the polarity of the tissue reorients during shear flow. Our simple mechanisms for ordering can account for the processes observed during development of the Drosophila wing

Dynamics of Cell Packing and Polar Order in Developing Epithelia

During development, organs with different shape and functionality form from a single fertilized egg cell. Mechanisms that control shape, size and morphology of tissues pose challenges for developmental biology. These mechanisms are tightly controlled by an underlying signaling system by which cells communicate to each other. However, these signaling networks can affect tissue size and morphology through limited processes such as cell proliferation, cell death and cell shape changes,which are controlled by cell mechanics and cell adhesion. One example of such a signaling system is the network of interacting proteins that control planar polarization of cells. These proteins distribute asymmetrically within cells and their distribution in each cell determines of the polarity of the neighboring cells. These proteins control the pattern of hairs in the adult Drosophila wing as well as hexagonal repacking of wing cells during development. Planar polarity proteins also control developmental processes such as convergent-extension. We present a theoretical study of cell packing geometry in developing epithelia. We use a vertex model to describe the packing geometry of tissues, for which forces are balanced throughout the tissue. We introduce a cell division algorithm and show that repeated cell division results in the formation of a distinct pattern of cells, which is controlled by cell mechanics and cell-cell interactions. We compare the vertex model with experimental measurements in the wing disc of Drosophila and quantify for the first time cell adhesion and perimeter contractility of cells. We also present a simple model for the dynamics of polarity order in tissues. We identify a basic mechanism by which long-range polarity order throughout the tissue can be established. In particular we study the role of shear deformations on polarity pattern and show that the polarity of the tissue reorients during shear flow. Our simple mechanisms for ordering can account for the processes observed during development of the Drosophila wing

Data from: Mutation is a sufficient and robust predictor of genetic variation for mitotic spindle traits in Caenorhabditis elegans

Different types of phenotypic traits consistently exhibit different levels of genetic variation in natural populations. There are two potential explanations: either mutation produces genetic variation at different rates, or natural selection removes or promotes genetic variation at different rates. Whether mutation or selection is of greater general importance is a longstanding unresolved question in evolutionary genetics. We report mutational variances (VM) for 19 traits related to the first mitotic cell division in C. elegans, and compare them to the standing genetic variances (VG) for the same suite of traits in a worldwide collection C. elegans. Two robust conclusions emerge. First, the mutational process is highly repeatable: the correlation between VM in two independent sets of mutation accumulation lines is ~0.9. Second, VM for a trait is a good predictor of VG for that trait: the correlation between VM and VG is ~0.9. This result is predicted for a population at mutation-selection balance; it is not predicted if balancing selection plays a primary role in maintaining genetic variation

Scaling, Selection, and Evolutionary Dynamics of the Mitotic Spindle

Background Cellular structures such as the nucleus, Golgi, centrioles, and spindle show remarkable diversity between species, but the mechanisms that produce these variations in cell biology are not known. Results Here we investigate the mechanisms that contribute to variations in morphology and dynamics of the mitotic spindle, which orchestrates chromosome segregation in all Eukaryotes and positions the division plane in many organisms. We use high-throughput imaging of the first division in nematodes to demonstrate that the measured effects of spontaneous mutations, combined with stabilizing selection on cell size, are sufficient to quantitatively explain both the levels of within-species variation in the spindle and its diversity over ∼100 million years of evolution. Furthermore, our finding of extensive within-species variation for the spindle demonstrates that there is not just one “wild-type” form, rather that cellular structures can exhibit a surprisingly broad diversity of naturally occurring behaviors. Conclusions Our results argue that natural selection acts predominantly on cell size and indirectly influences the spindle through the scaling of the spindle with cell size. Previous studies have shown that the spindle also scales with cell size during early development. Thus, the scaling of the spindle with cell size controls its variation over both ontogeny and phylogeny.Molecular and Cellular Biolog

Mitotic spindle traits in C. elegans

The data included in this file are the raw measurements for 19 traits associated with the first mitotic cell division. The first column is the Species (C. elegans), the second column is the Genotype (N2 MA line, PB306 MA line, or wild isolate); the third column is the Strain designation, the fourth column is the Treatment (MA control, MA line, or wild isolate), the fifth column is the Line number, the sixth column is the Replicate number, and the remaining columns are the traits. The traits are described in the Methods and Materials of the associated publication

Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair

Recent work done exclusively in tissue culture cells revealed that the nuclear envelope (NE) ruptures and repairs in interphase. The duration of NE ruptures depends on lamins; however, the underlying mechanisms and relevance to in vivo events are not known. Here, we use the Caenorhabditis elegans zygote to analyze lamin’s role in NE rupture and repair in vivo. Transient NE ruptures and subsequent NE collapse are induced by weaknesses in the nuclear lamina caused by expression of an engineered hypomorphic C. elegans lamin allele. Dynein-generated forces that position nuclei enhance the severity of transient NE ruptures and cause NE collapse. Reduction of dynein forces allows the weakened lamin network to restrict nucleo–cytoplasmic mixing and support stable NE recovery. Surprisingly, the high incidence of transient NE ruptures does not contribute to embryonic lethality, which is instead correlated with stochastic chromosome scattering resulting from premature NE collapse, suggesting that C. elegans tolerates transient losses of NE compartmentalization during early embryogenesis. In sum, we demonstrate that lamin counteracts dynein forces to promote stable NE repair and prevent catastrophic NE collapse, and thus provide the first mechanistic analysis of NE rupture and repair in an organismal context