Biomedical subjects

Marc R Freeman

Publications and source records attributed to Marc R Freeman.

6 recordsLinked to original sources

PubMed2006

The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons.

Neuron-glia communication is central to all nervous system responses to trauma, yet neural injury signaling pathways remain poorly understood. Here we explore cellular and molecular aspects of neural injury signaling in Drosophila. We show that transected Drosophila axons undergo injury-induced degeneration that is morphologically similar to Wallerian degeneration in mammals and can be suppressed by the neuroprotective mouse Wlds protein. Axonal injury elicits potent morphological and molecular responses from Drosophila glia: glia upregulate expression of the engulfment receptor Draper, undergo dramatic changes in morphology, and rapidly recruit cellular processes toward severed axons. In draper mutants, glia fail to respond morphologically to axon injury, and severed axons are not cleared from the CNS. Thus Draper appears to act as a glial receptor for severed axon-derived molecular cues that drive recruitment of glial processes to injured axons for engulfment.

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PubMed2006

Glial cell biology in Drosophila and vertebrates.

Glia are the most abundant cell type in the mammalian nervous system and they have vital roles in neural development, function and health. However our understanding of the biology of glia is in its infancy. How do glia develop and interact with neurons? How diverse are glial populations? What are the primary functions of glia in the mature nervous system? These questions can be addressed incisively in the Drosophila nervous system--this contains relatively few glia, which are well-defined histologically and amenable to powerful molecular-genetic analyses. Here, we highlight several developmental, morphological and functional similarities between Drosophila and vertebrate glia. The striking parallels that emerge from this comparison argue that invertebrate model organisms such as Drosophila have excellent potential to add to our understanding of fundamental aspects of glial biology.

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PubMed2006

Sculpting the nervous system: glial control of neuronal development.

Glial cells are not passive spectators during nervous system assembly, rather they are active participants that exert significant control over neuronal development. Well-established roles for glia in shaping the developing nervous system include providing trophic support to neurons, modulating axon pathfinding, and driving nerve fasciculation. Exciting recent studies have revealed additional ways in which glial cells also modulate neurodevelopment. Glial cells regulate the number of neurons at early developmental stages by dynamically influencing neural precursor divisions, and at later stages by promoting neuronal cell death through engulfment. Glia also participate in the fine sculpting of neuronal connections by pruning excess axonal projections, shaping dendritic spines, and secreting multiple factors that promote synapse formation and functional maturation. These recent insights provide further compelling evidence that glial cells, through their diverse cellular actions, are essential contributors to the construction of a functionally mature nervous system.

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PubMed2005

Glial (and neuronal) cells missing.

The Glial cells missing transcription factor is necessary and sufficient to induce glial-cell fates in the Drosophila embryonic nervous system. A study by Chotard et al. in this issue of Neuron reveals that this "master regulator" of glial cell fate specification is also required (gasp!) to generate neurons.

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PubMed2005

Glial control of synaptogenesis.

Though all communication between neurons occurs through synapses, we know surprisingly little about the mechanisms inducing their formation. In this issue of Cell, Barres and colleagues (Christopherson et al., 2005) demonstrate that glial-derived thrombospondins and additional soluble glial-secreted factors regulate synapse assembly and functional maturation.

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PubMed2003

Unwrapping glial biology: Gcm target genes regulating glial development, diversification, and function.

Glia are the most abundant cell type in the mammalian brain. They regulate neuronal development and function, CNS immune surveillance, and stem cell biology, yet we know surprisingly little about glia in any organism. Here we identify over 40 new Drosophila glial genes. We use glial cells missing (gcm) mutants and misexpression to verify they are Gcm regulated in vivo. Many genes show unique spatiotemporal responsiveness to Gcm in the CNS, and thus glial subtype diversification requires spatially or temporally restricted Gcm cofactors. These genes provide insights into glial biology: we show unc-5 (a repulsive netrin receptor) orients glial migrations and the draper gene mediates glial engulfment of apoptotic neurons and larval locomotion. Many identified Drosophila glial genes have homologs expressed in mammalian glia, revealing conserved molecular features of glial cells. 80% of these Drosophila glial genes have mammalian homologs; these are now excellent candidates for regulating human glial development, function, or disease.

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