Time-lapse and cell ablation reveal the role of cell interactions in fly glia migration and proliferation
Institut de Génétique et Biologie Moléculaire et Cellulaire, IGBMC/CNRS/ULP/INSERM - BP 10142, ILLKIRCH, C. U. de Strasbourg 67404, France. Development
(Impact Factor: 6.46).
11/2004; 131(20):5127-38. DOI: 10.1242/dev.01398
Migration and proliferation have been mostly explored in culture systems or fixed preparations. We present a simple genetic model, the chains of glia moving along fly wing nerves, to follow such dynamic processes by time-lapse in the whole animal. We show that glia undergo extensive cytoskeleton and mitotic apparatus rearrangements during division and migration. Single cell labelling identifies different glia: pioneers with high filopodial, exploratory, activity and, less active followers. In combination with time-lapse, altering this cellular environment by genetic means or cell ablation has allowed to us define the role of specific cell-cell interactions. First, neurone-glia interactions are not necessary for glia motility but do affect the direction of migration. Second, repulsive interactions between glia control the extent of movement. Finally, autonomous cues control proliferation.
Available from: Tripti Gupta-Bosch
- "Journal of Cell Science ( 2015 ) 128 , 900 – 912 doi : 10 . 1242 / jcs . 157974 cells are necessary to drag the long chain made of 60 – 70 cells , spanning over almost 800 mm . Moreover , the long glial chain relies on relay mechanisms and homeostatic interactions to migrate efficiently ( Aigouy et al . , 2004 ; Berzsenyi et al . , 2011 ) . As proposed by Montell and collaborators ( Cai et al . , 2014 ) , various mechanisms can account for the diversity of morphogenetic movements ; therefore , understanding the signaling cascades mediated by cadherins will require the analysis of different collectives ( chains , clusters , streams , sheets an"
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ABSTRACT: Cell migration is an essential and highly regulated process. During development, glia and neurons migrate over long distances, in most cases collectively, to reach their final destination and build the sophisticated architecture of the nervous system, the most complex tissue of the body. Collective migration is highly stereotyped and efficient, defects in the process leading to severe human diseases that include mental retardation. This dynamic process entails extensive cell communication and coordination, hence the real challenge is to analyze it in the whole organism and at cellular resolution. We here investigate the impact of the N-cadherin adhesion molecule on collective glial migration using the Drosophila developing wing and cell-type specific manipulation of gene expression. We show that N-cadherin timely accumulates in glial cells and that its levels affect migration efficiency. N-cadherin works as a molecular brake in a dosage dependent manner by negatively controlling actin nucleation and cytoskeleton remodeling through α/β catenins. This is the first in vivo evidence for N-cadherin negatively and cell autonomously controlling collective migration.
Available from: Christian M von Hilchen
- "Ablation experiments were performed to confirm that additional glial nuclei along the NER of larvae originate from ePG2. High-energy UV irradiation was used to eliminate ePG2 in the embryo, a method previously used to ablate glial cells in the developing fly wing (Aigouy et al., 2008; Aigouy et al., 2004). "
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ABSTRACT: One of the numerous functions of glial cells in Drosophila is the ensheathment of neurons to isolate them from the potassium-rich haemolymph, thereby establishing the blood-brain barrier. Peripheral nerves of flies are surrounded by three distinct glial cell types. Although all embryonic peripheral glia (ePG) have been identified on a single-cell level, their contribution to the three glial sheaths is not known. We used the Flybow system to label and identify each individual ePG in the living embryo and followed them into third instar larva. We demonstrate that all ePG persist until the end of larval development and some even to adulthood. We uncover the origin of all three glial sheaths and describe the larval differentiation of each peripheral glial cell in detail. Interestingly, just one ePG (ePG2) exhibits mitotic activity during larval stages, giving rise to up to 30 glial cells along a single peripheral nerve tract forming the outermost perineurial layer. The unique mitotic ability of ePG2 and the layer affiliation of additional cells were confirmed by in vivo ablation experiments and layer-specific block of cell cycle progression. The number of cells generated by this glial progenitor and hence the control of perineurial hyperplasia correlate with the length of the abdominal nerves. By contrast, the wrapping and subperineurial glia layers show enormous hypertrophy in response to larval growth. This characterisation of the embryonic origin and development of each glial sheath will facilitate functional studies, as they can now be addressed distinctively and genetically manipulated in the embryo.
Available from: Leslie P Tolbert
- "Collective or chain migration is a fundamental feature of migration in Drosophila wing and peripheral nerve (Giangrande, 1994; Sepp et al., 2000; Aigouy et al., 2004; von Hilchen et al., 2008), in the Manduca enteric nervous system (Copenhaver and Taghert, 1989; Wright and Copenhaver, 2000) and in zebrafish peripheral nerves (Kucenas et al., 2008). In the moth antennal nerve, AN glial cells often appear in chains in vivo especially at the early stages of migration although the dimensions of the nerve and the pattern of glial process extension indicate that chaining along cannot be responsible for continuous ensheathment of axon bundles. "
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ABSTRACT: In adult olfactory nerves of mammals and moths, a network of glial cells ensheathes small bundles of olfactory receptor axons. In the developing antennal nerve (AN) of the moth Manduca sexta, the axons of olfactory receptor neurons (ORNs) migrate from the olfactory sensory epithelium toward the antennal lobe. Here we explore developmental interactions between ORN axons and AN glial cells. During early stages in AN glial-cell migration, glial cells are highly dye coupled, dividing glia are readily found in the nerve and AN glial cells label strongly for glutamine synthetase. By the end of this period, dye-coupling is rare, glial proliferation has ceased, glutamine synthetase labeling is absent, and glial processes have begun to extend to enwrap bundles of axons, a process that continues throughout the remainder of metamorphic development. Whole-cell and perforated-patch recordings in vivo from AN glia at different stages of network formation revealed two potassium currents and an R-like calcium current. Chronic in vivo exposure to the R-type channel blocker SNX-482 halted or greatly reduced AN glial migration. Chronically blocking spontaneous Na-dependent activity by injection of tetrodotoxin reduced the glial calcium current implicating an activity-dependent interaction between ORNs and glial cells in the development of glial calcium currents.
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