A role for programmed cell death during early neurogenesis in xenopus

In vertebrates, little is known on the role of programmed cell death (PCD) occurring within the population of dividing neural precursors and newly formed neuroblasts during early neural development. During primary neurogenesis, PCD takes place within the neuroectoderm of Xenopus embryos in a reproducible stereotypic pattern, suggesting a role for PCD during the early development of the CNS. We find that the spatio-temporal pattern of PCD is unaffected in embryos in which cell proliferation has been blocked and whose neuroecotoderm contains half the normal number of cells. This shows that PCD is not dependent on cell division. It further suggests that PCD does not solely function to regulate absolute cell numbers within the neuroectoderm. We demonstrate that PCD can be reproducibly inhibited in vivo during primary neurogenesis by the overexpression of human Bcl-2. Following PCD inhibition, normal neurogenesis is disrupted, as seen by the expansion of the expression domains of XSox-2, XZicr-2, XNgnr-1, XMyT-1, and N-Tubulin, XNgnr-1 being the most affected. PCD inhibition, however, did not affect the outcome of lateral inhibition. We propose, then, that PCD regulates primary neurogenesis at the level of neuronal determination.     

UNC-52/perlecan affects gonadal leader cell migrations in C. elegans hermaphrodites through alterations in growth factor signaling

The unc-52 gene of Claenorhabditis elegans encodes a homologue of the basement membrane heparan sulfate proteoglycan perlecan. Viable alleles reduce the abundance of UNC-52 in late larval stages and increase the frequency of distal tip cell (DTC) migration defects caused by mutations disrupting the UNC-6/netrin guidance system. These unc-52 alleles do not cause circumferential DTC migration defects in an otherwise wild-type genetic background. The effects of unc-52 mutations on DTC migrations are distinct from effects on myofilament organization and can be partially suppressed by mutations in several genes encoding growth factor-like molecules, including EGL-17/FGF, UNC-129/TGF-beta, DBL-1/TGF-beta, and EGL-20/WNT. We propose that UNC-52 serves dual roles in C. elegans larval development in the maintenance of muscle structure and the regulation of growth factor-like signaling pathways.     

An increase in surface area is not required for cell division in early sea urchin development

Cell division requires an increase in surface area to volume ratio. During early development, surface area can increase, volume can decrease, or surface topography can be optimized to allow for division. While exocytosis is thought to be essential for division [Mol. Biol. Cell 10 (1999), 2735; Proc. Natl. Acad. Sci. USA 99 (2002), 3633], exocytosis doesn't always yield an increase in surface area [Proc. Natl. Acad. Sci. USA 79 (1982), 6712]. We used multiphoton laser scanning microscopy, fluorescence spectroscopy, and electron microscopy to monitor membrane trafficking, surface area, volume, and surface topography during early sea urchin development. Despite extensive membrane trafficking monitored by FM 1-43 fluorescence, we find that the net surface area of the embryo does not change prior to the eight-cell stage. During this period, embryo volume decreases by 15%, and microvilli disappear from interior facing membrane segments. Thus, the first three cell divisions utilize residual membrane liberated by decreasing cytoplasmic volume, and reducing microvilli density on interior facing membranes. Only after the eight-cell stage was a net increase in FM 1-43 fluorescence from the embryo surface detected. Our data suggest that compensatory endocytosis is downregulated after this developmental stage to yield an increase in surface area for cell division.     

The evolution of female multiple mating in social hymenoptera

Abstract The evolution of female multiple mating is a highly controversial topic, especially in social insects. Here we analyze, using comparative analyses and simulation models, the merits of two major contending hypotheses for the adaptive value of polyandry in this group. The hypotheses maintain that, respectively, the resulting genotypic diversity among offspring within a colony: (1) mitigates against the effects of parasites; or (2) favors adaptive division of labor. Only two of 11 phylogenetically uncontrolled comparative analyses supported an association between polyandry and the complexity of division of labor (measured here using worker caste polymorphism or polyethism) as proposed by hypothesis 2, and after controlling for phylogeny there were no significant associations. In contrast, a previous study demonstrated such an association for parasite load as expected under hypothesis 1. In addition, we used simulation models to track the spread of an initially rare allele for double mating in a population of single-mating alleles, thus analyzing the crucial first step from monandry to polyandry. We find that double mating evolves consistently under antagonistic coevolution given that parasites exert sufficient selection intensity. In contrast, selection for enhanced division of labor resulted in only an erratic appearance of polyandry in highly (and mostly negatively) autocorrelated environments where no coevolutionary dynamics were allowed. Together, we interpret these results to suggest that parasites, and the antagonistic coevolutionary pressures they exert, may play an important role in the evolution of polyandry in social hymenopteran populations.     

The spatial organization of centromeric heterochromatin during normal human lymphopoiesis: evidence for ontogenically determined spatial patterns

It is believed that pericentromeric heterochromatin may play a major role in the epigenetic regulation of gene expression. We have previously shown that centromeres in human peripheral blood cells aggregate into distinct "myeloid" and "lymphoid" spatial patterns, suggesting that the three-dimensional organization of centromeric heterochromatin in interphase may be ontogenically determined during hematopoietic differentiation. To investigate this possibility, the spatial patterns of association of different centromeres were analyzed in hematopoietic progenitors and compared with those in early-B and early-T cells, mature B and T lymphocytes, and, additionally, mature granulocytes and monocytes. We show that those patterns change during lymphoid differentiation, with major spatial arrangements taking place at different stages during T and B cell differentiation. Heritable patterns of centromere association are observed, which can occur either at the level of the common lymphoid progenitor, or in early-T or early-B committed cells. A correlation of the observed patterns of centromere association with the gene content of the respective chromosomes further suggests that the variation in the composition of these heterochromatic structures may contribute to the dynamic relocation of genes in different nuclear compartments during cell differentiation, which might have functional implications for cell-stage-specific gene expression.     

Phosphorylation-dependent structural alterations in the small hsp30 chaperone are associated with cellular recovery

Small heat shock proteins (hsps) act as molecular chaperones by preventing the thermal aggregation and unfolding of cellular protein; however, the manner by which cells regulate chaperone activity remains unclear. In the present study, we examined the role of phosphorylation on the chaperone function of the Xenopus small hsp30. Both heat stress and sodium arsenite treatment in A6 cells resulted in a rapid activation of p38alpha and MAPKAPK-2. Surprisingly, the association of MAPKAPK-2 with hsp30 and its subsequent phosphorylation were more prevalent during recovery after heat stress. Treatment of A6 cells with SB203580, an inhibitor of the p38 MAP kinase pathway, resulted in a loss of hsp30 phosphorylation. Phosphorylation resulted in the formation of smaller multimeric hsp30 complexes and resulted in a significant loss of secondary structure. Consequently the phosphorylation-induced structural changes severely compromised the ability of hsp30 to prevent the heat-induced aggregation of citrate synthase and luciferase in vitro. We confirmed that the loss of chaperone activity was coincident with an attenuated binding of phosphorylated hsp30 with target proteins. Our data suggest that phosphorylation may be necessary to regulate the post-heat stress molecular chaperone activity of hsp30.