XI European Meeting on Glial Cell Function in Health and Disease

Overview Session Overview Sessionprint print  

July 3, 2013 - Room 5 3:15pm - 5:15pm
Symposium 5: Genetic Dissection of Glial Cell Development and Function in Drosophila

Christian Klämbt (Münster)


Neuron-glia interactions through the Heartless FGF receptor signaling pathway mediate morphogenesis of Drosophila astrocyte-like glia

*Marc R. Freeman 1 , Tobias Stork 1
1 University of Massachusetts, Medical School, Dept of Neurobiology, Worcester, MA, United States
Abstract text :

Astrocytes are critically important for neural circuit assembly and function.  Mammalian protoplasmic astrocytes develop a dense ramified meshwork of cellular processes with which they form intimate contacts with neuronal cell bodies, neurites and synapses.  This close neuron-glia morphological relationship is essential for astrocyte function, but it remains unclear how astrocytes establish their intricate morphology, organize unique spatial domains, and associate with neurons and synapses in vivo.  We have characterized a Drosophila glial subtype that shows striking morphological and functional similarities to mammalian astrocytes.  Fly astrocyte-like glia have a highly tufted morphology, associate closely with CNS synapses, and express neurotransmitter transporters for GABA (Gat) and glutamate (EAAT1).  We find that loss of Gat function or ablation of astrocyte-like glia leads to profound defects in larval behavior and early animal lethality.  We further demonstrate the Fibroblast growth factor (FGF) receptor Heartless autonomously controls astrocyte-like glial membrane growth during development, and the neuron-derived FGF ligands Pyramus and Thisbe direct astrocyte processes to ramify specifically in synaptic areas in the nervous system.  Finally, we demonstrate the shape and size of individual astrocyte-like glia are not strictly stereotyped but are dynamically shaped through a combination of inhibitory astrocyte-astrocyte interactions, cell competition and Heartless FGF signaling.  Our data demonstrate a conserved requirement for an astrocyte-like cell type in even relatively simple nervous systems and identify the Heartless FGF signaling cascade as a critical regulator of astrocyte morphological elaboration in vivo.


A Gene Network Underlying the Glial Regenerative Response to central nervous system injury in fruit-flies and mammals

Kentaro Kato 1 , *Alicia Hidalgo 1
1 University of Birmingham, , Birmingham, United Kingdom
Abstract text :

Organisms are structurally robust, as cells accommodate changes preserving integrity and function. The molecular mechanisms underlying such plasticity are unknown, but can be investigated by probing cellular responses to injury. Injury to the central nervous system (CNS) induces glial proliferation, enabling axonal re-enwrapment and partial functional recovery. This glial regenerative response is found across species, suggesting a common genetic mechanism. We use Drosophila to uncover a gene network controlling this response. It enables glia to divide upon injury, restore arrest preventing tumorigenesis, and differentiate. It is homeostatic as two cell cycle activators promote the expression of a cell cycle inhibitor, providing negative feedback on cell division. Pros is essential for glial differentiation, promoting debris clearance and axonal enwrapment. This gene network can promote regeneration of the glial lesion and neuropile repair. Our recent findings indicate that at least some aspects of this gene network discovered in fruit-flies has been evolutionarily conserved and operates also in mammals. We will present our latest findings testing this gene network in the mouse.


Vesicle release mechanisms and glia-to-neuron signaling are critical in Drosophila for astrocyte regulation of circadian behavior

*F.Rob Jackson 1 , Fanny Ng 1 , Sukanya Sengupta 1 , Samantha You 1
1 Tufts Univ. Sch. Med., , Boston, United States
Abstract text :

Studies in Drosophila and mammals indicate that glial astrocytes are critical for the regulation of neuronal synaptic activity and complex behaviors. For example, we have shown in Drosophila that glial cells are important components of the neural circuitry controlling circadian locomotor activity rhythms (Ng et al., Curr. Biol., 2011). Conditional genetic perturbation of vesicle trafficking and calcium homeostasis in Drosophila astrocytes revealed that: 1) they can regulate circadian behavior by modulating transport and/or release of a circadian neurotransmitter (PDF); 2) the glial regulation of rhythms is dependent on glial calcium stores; 3) astrocytes, but not other glial classes, can regulate circadian behavior.


In more recent studies, we have begun to examine the mechanisms of glia-to-neuron communication in the regulation of circadian behavior. For example, we have shown that genetic manipulations affecting astrocyte vesicular release mechanisms result in arrhythmic circadian behavior. To better understand how such manipulations affect excitability of circadian clock neurons, we are employing calcium imaging techniques to examine glia-to-neuron communication in adult Drosophila brain preparations. Finally, we have recently utilized Translating Ribosome Affinity Purification (TRAp) techniques for cell-specific translational profiling of clock neurons and we are now employing these techniques to molecularly profile Drosophila astrocytes. Our goal is to define all translated RNAs of fly astrocytes so as to facilitate targeted genetic screens for factors that regulate glia-to-neuron communication.


Development and function of Drosophila wrapping glia

*Christian Klämbt 1 , Silke Thomas 1 , Nils Otto 1 , Steffi Schrettenbrunner 1 , Astrid Weiler 1 , Stefanie Limmer 1
1 Universität Münster, Institut für Neuro- und Verhaltensbiologie, Münster, Germany
Abstract text :

Glial cells support neurons during development as well as in the established nervous system. For example, in the vertebrate nervous system, astrocytes modulate synaptic functions in several ways. On one side, astrocytes buffer the ionic milieu around synapses and recycle neurotransmitters, on the other side, they are able to provide energy to neurons assuring their function. Although many aspects of how glial cells modulate neuronal functionality are know, the underlying gene functions are mostly elusive. 

In the Drosophila nervous system, glial cells exert similar tasks as compared to their vertebrate counterparts.  Within the brain, several glial cells associate with axons, dendrites and synapses. Two main classes of these neuropil associated glial cells have been described, which can be targeted by promoter elements derived from the nervana2 or the alrm locus. To identify genes required in the different glial cells for normal function of the nervous system we performed several cell-type specific RNAi-based gene silencing screens. This led to the identification of several candidate genes that result in locomotion defects when exclusively silenced in nervana2 or alrm expressing neuropil glial cells. Three of the candidate genes identified by this screen encode membrane associated proteins. The gene rumpel encodes a  protein with homology to monocarboxylate transporting proteins and thus might act during energy homeostasis in the neuropil glia. In Drosophila, neuronal energy homeostasis is closely linked to glial cells since the so-called subperineurial glial cells form the blood brain barrier and therefore regulate the entry of nutrients into the nervous system. We will briefly review our progress in dissecting carbohydrate uptake into the nervous system.