Marc Freeman, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Neurobiology

Other Affiliation(s):
   Program in Neuroscience

Unwrapping Glial Biology in Drosophila

Neurons are not alone in the nervous system—90% of the cells in your brain are glia.  This dynamic cell type has an extraordinary range of functions including regulation of neural stem cell biology, axon pathfinding, neuronal survival, and synapse formation and efficacy.  Despite many decades of work describing exciting roles for glia in the nervous system, we know surprisingly little about the molecular pathways mediating glial biology in any organism. 

The major goal of our work is to understand glial development and function at the molecular and cellular level.  We use Drosophila as it offers an excellent opportunity to study glial biology in a genetically tractable organism (see Figure 1).  In Drosophila, nearly all embryonic glial lineages have been completely defined from precursor to post-mitotic glia.  Drosophila offers an array of powerful genetic and molecular tools for incisive analysis of gene function in vivo.  We believe our work in flies should teach us a great deal about mammalian glia as the major classes of glia found in both vertebrates and insects are strikingly similar by morphological, functional, and molecular criteria. 

We have recently used a combination of powerful genomic approaches—computational binding site search algorithms, cDNA microarrays, and database mining—to identify a large collection of genes specifically expressed in Drosophila embryonic glia.  These genes encode a variety of types of molecules: secreted growth factors, transmembrane receptors, cytoskeletal scaffolding proteins, and several novel genes.  This collection serves the dual purpose of providing a wealth of markers for glial subtypes or specific developmental events, and many interesting candidate genes for functional studies.  We are now using an array of tools including genetics, cell biology, molecular biology, and microscopy (light, confocal, and electron) to define the functional requirements for a subset of these genes in glial development in the Drosophila embryonic nervous system.

Are the molecular pathways driving fly glial development involved in glial development in other organisms?  To answer this question we are collaborating with the laboratory of David Rowitch (Dana-Farber) to perform a large-scale comparative analysis of gene expression patterns in Drosophila and mouse glia.  Through this work we are finding for many identified Drosophila glial genes that the vertebrate sequence orthologues appear to be expressed in mammalian glial lineages.  These data indicate a high degree of overlap in the molecular expression patterns of fly and mouse glia, and suggest our studies in Drosophila are poised to provide key insights into mammalian glial development, function, and disease.

Figure
1)  Pattern and morphology of Drosophila embryonic glia.  Ventral view of a late stage Drosophila embryo where glial nuclei are stained in red, and glial membranes are stained green.  Embryonic glia ensheath the entire nervous system.  Their functions include governing axon pathfinding and fasciculation, providing trophic support to promote neuronal survival, and acting as CNS immune cells.

Research Articles

Ziegenfuss, J.S., Biswas, R., Avery, M.A., Sheehan, A.E., Stanley, E.R., and M.R. Freeman  (2008)  Draper-dependent glial phagocytic activity is mediated by Src family kinase signaling cascade.  Nature, 453: 935-9.

Beach, M., MacDonald, J., Porpiglia, E., Sheehan, A.E., Watts, R.E., and M.R. Freeman.  (2006) The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons.  Neuron, 50, 869-881.

Freeman, M.R., Delrow, J., Kim, J., Johnson, E., and C.Q. Doe  (2003)  Unwrapping glial biology:  Gcm target genes regulating glial development, diversification, and function.  Neuron  38, 567-580.

Freeman, M.R., and C.Q. Doe (2001) Asymmetric Prospero localization is required to generate mixed neuronal/glial lineages in the Drosophila CNS.  Development 128, 4103-12.

Freeman, M.R., A. Dobritsa, P. Gaines, W.A. Segraves, and J.R. Carlson (1999)  The dare gene: Steroid hormone production, olfactory behavior, and neural degeneration in Drosophila.  Development 126, 4591-602.

Buszczak, M., M.R. Freeman, J.R. Carlson, M. Bender, L. Cooley, and W.A. Segraves (1999)  Ecdysone response genes govern egg chamber development during mid-oogenesis in Drosophila.  Development 126, 4581-4589.

Clyne, P.J., C.G. Warr, M.R. Freeman, D. Lessing, J. Kim, and J.R. Carlson (1999) A novel family of divergent seven-transmembrane proteins: candidate odorant receptors in Drosophila.  Neuron, 22, 327-338.

Review Articles

Logan, M.A., and M.R. Freeman (2007)  The scoop on the fly brain:  Glial engulfment functions in Drosophila.  Neuron Glia Biology 3(1) 63-74.

Freeman, M.R., and J. Doherty (2006)  Glial cell biology in Drosophila and mammals.  Trends in Neurosciences 29, 82-90.

Freeman, M.R.  (2006)  Sculpting the nervous system:  Glial control of neuronal development.  Current Opinion in Neurobiology 16, 119-125.

Freeman, M.R., and C.Q. Doe (2001)  Moving muscle:  Jeb signaling in Drosophila.  Developmental Cell 1, 587-8.

Minireviews/Previews

Emery, P., and M.R. Freeman (2007)  Glia got rhythm.  Neuron 55, 337-339.

Freeman, M.R. (2005)  Glial (and neuronal) cells missing.  Neuron 48, 163-165.

Freeman, M.R.  (2005)  Glial control of synaptogenesis.  Cell  120, 292-293.

Freeman, M.R., and C.Q. Doe (2001)  Moving muscle: Jeb signaling in Drosophila.  Developmental Cell 1, 587-8.

Office: 719
Phone: 508-856-6136
E-mail: Marc.Freeman@umassmed.edu
Keywords: Neurobiology

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