[
International Worm Meeting,
2021]
Interactions between neurons and glia are essential for all normal nervous system functions. C. elegans glia have similar types of function as mammalian glia and are now established as a powerful genetic model to study glial biology. The adult hermaphrodite nervous system contains 302 neurons and 56 glia, with at least some of the glia shown to profoundly impact associated neuron shape and associated animal behaviors. Adult males have an additional 36 glia and 89 neurons, many of which control male mating-related behaviors. A major limitation in studying C. elegans glia functions is the lack of cell-type specific markers for each glial subtype in the adult worm, and a global comparative assessment of glial functional and molecular heterogeneity. Further, each C. elegans glia is born of an invariant developmental lineage and makes invariant neuron-contact. This not only makes the nematode a powerful model to study glia-neuron interactions, but also suggests a unique advantage of this model to examine glia at single-cell and molecular detail. Addressing this gap, we present our single nuclear RNAseq (snRNAseq) studies on adult C. elegans glia across the entire nervous system. We have done these studies in three settings, (1) young adult hermaphrodites, (2) young adult males, and (3) aged hermaphrodites. These data will be compiled and shared as a searchable three-dimensional online atlas of adult glial gene expression as a community resource. Our datasets allow us to now create a gene expression and marker atlas of glia at single cell resolution. Our preliminary data reveal 30 clusters, hinting already at interesting biological insights into glial heterogeneity. Further, studies in our lab and others have found that multiple glial cues within a single glia, the amphid sheath (AMsh), regulate neuron morphology and sensory behaviors, with age-related effects. Therefore, in addition to describing glia-specific and glial subclass markers, we are currently validating our datasets functionally in similar assays, including neural aging. The aim of our studies is to expand our understanding of how different glia execute these regulatory neural functions across cell-type, sex and animal aging.
Atwell, K., Osborne, J.M., Qin, Z., Kugler, H., Gavaghan, D.J., Hubbard, E.J.A.
[
International Worm Meeting,
2015]
Understanding germline development as a whole can be challenging. The combination of cell-cell signalling, systemic effects, gonad growth, cell mechanics and movement all complicate the link between individual cell behaviour and whole organ properties. Computer models provide one approach to address this challenge. They can also provide testable predictions and can aid in interpreting data.We have produced a dynamic, 3D model of the C. elegans germ line that builds on previous work (Setty et al. 2012) by incorporating both the mechanical forces between cells and a model of the decision-making molecular processes at work inside cells. The mechanics component of the model was built using the software Chaste (Cancer Heart and Soft Tissue Environment; Mirams et al. 2013) and represents cells as deformable spheres that exert force on each other when they overlap. The behaviour of individual germ cells is determined by a Statechart (Harel 1987), a formalism for representing complex systems that is widely used in engineering and computer science. By applying a growing gonad boundary condition that forms along the path of the DTC we were able to simulate both larval development and adult homeostasis in a single program run.Our simulations produce a reasonable agreement with experiment across a range of measured germ line properties, including ovulation rate, sperm count and total cell count. To achieve this fit, we found that two new biological properties had to be incorporated into the model. First, we include a period of "stretching" growth during late L4, in which the turn region of the gonad moves centrifugally. We measured this growth in larval stage worms and speculate that it may result from germ cell pressure inside the gonad. Second, we included contact inhibition among proliferative germ cells. This robustly stabilized proliferative cell numbers at a reasonable level compared to attempts to balance a fixed cell proliferation rate and a fixed death rate. Finally, we also demonstrate in silico cell tracking and lineage labelling between L3 and adulthood.