Charlton-Perkins Lab

Department of Biology, Miami University, Oxford, Ohio

Department of Biology

Miami University

Mark Charlton-Perkins, PhD

Assistant Professor

390 Pearson Hall

Biology

Miami University

Oxford, OH

Office Phone : 513-529-3175

Email: charltm@miamioh.edu

For more than 150 years, glial cells have been known to be a major part of neural tissue. Still, their role as the primary regulators of neural system development and function has only recently been understood. As glial cells' roles in neural homeostasis, metabolism, physiology, and structure become more appreciated, research into their development has increased. Genetic and microarray studies have identified several genes involved in glial cell proliferation, specification, activation, and regeneration. However, compared to their neuronal counterparts, which are much more numerous in the human brain, we still know very little about the final anatomical differentiation of glial cells. There are three active areas of investigation currently being pursued in my lab that focus either on the development or diseases in the nervous system.

We and others extensively studied the morphological and physiological changes of zebrafish retinal glia over their development, which has allowed us to categorize these cells into at least six progressive stages (Charlton-Perkins et al., McDonald et al., Wang et al.,). Using temporal transcriptomics combined with novel CRISPR strategies, we have developed methods to conduct large-scale reverse genetic screens and, for the first time, test the functions of these differentiation factors in mass. These developmental studies aim to identify evolutionarily conserved pathways responsible for both glial cell shape and the development of their mature physiologies. This research has far-reaching implications for our understanding of cellular evolution. It provides novel insights into the process of evolution and can influence studies on many genes related to neural diseases. In particular, we have developed disease models for Wolfram’s Disease, Neuromyelitis Optica, Neurofibromatosis type-1, and Myopia to explore further how these highly conserved molecular pathways are implicated in nervous system disease. This research could help identify the genetic basis of certain neurological disorders and provide new ways of treating them.

We are currently recruiting graduate students and post-docs (contact Dr C-P by email for details)

Positions in the Lab

Lab Gallery

The History of Glia

Active research areas in the Lab

Glial Morphology

Glial Evolution and Function

Glial Disease

Undergraduate Research

Publications

Positions in the Lab

Current Postdoctoral Position in Biotech Partnership to Study Myopia

We accept enquiries for graduate admissions in all the interdisciplinary graduate programs at the college of Arts and Sciences (https://miamioh.edu/cas/graduate-programs/biology/index.html). Equireries can be sent to Dr C-P (charltm@mimioh.edu).

Lab Gallery

The History of Glia

Glia were discovered over 150 years ago and their presence through the nervous system was documented repeatedly, most apparently by the researchers depicted above. However, the critical functions glia perform in the nervous system weren’t demonstrated until the 1960s by Holger Hyden and Stephen Kufflers. Still today, the amount we understand about the development or role in neurologic disease is relatively small compared to their neuronal counterparts.

Active research areas in the Lab

Glial Morphology

Drawings of retinal Müller glia from different animals done by the famous neurobiologist Ramon y Cajal from his 1893 publication “La rétine des vertébrés” published in La Cellule, 9 (1893), pp. 120-258. See our review on how glial morphology arises and our article on glial compartment formation in the publications section below.

We previously showed that stage-specific genetic enrichment determines Muller glia compartment morphology and this showed that detailed temporal transcriptomics is powerful for understanding cell morphogenesis (See Charlton-Perkins et al, 2019). The molecular mechanisms driving this morphologic diversity are mostly unknown. One objective in the lab is to use novel CRISPR strategies to continue exploring the molecular events underlying Muller glial morphology. (Center image modified from Charlton-Perkins et al, 2019. OLM - outer limiting membrane, OPL - outer plexiform layer, IPL - inner plexiform layer, ILM - inner limiting membrane)

Glial Evolution and Function

Müller glia are the most abundant in the retina and provide highly conserved structural and physiological support roles, but this area of research is still understudied. Our previous work provided the first temporally complete transcriptome of a differentiating retinal glial population and an in-depth reverse genetic analysis of how glial morphology arises. Our lab has developed a novel cell-specific gene repression approach in zebrafish that can be used to study the autonomous roles glia perform in the retina. We have also designed and generated several biosensor animals to study specific physiological functions like metabolism, ion maintenance and neurotransmitter recycling glia in-vivo. We use these new tools to analyze how particular physiology genes regulate adult glial functions.

The functions of glial (summerised above). When potassium maintenance is disrupted in Muller glia gliosis (glial inflammation) is frequently noted.

Potassium ion channel disruption leads to visual behavioural defects in fish embryos.

Glial Disease

Optic nerve dystrophies are among the most common form of severe vision loss. As glial cells' function in neural homeostasis, metabolism, physiology, and structure become increasingly appreciated, research into glial development has accelerated. There is still much to learn about glial morphogenesis, and there is a recognized gap in genetic knowledge between their specification and adult functions. In our lab, we study optic dystrophies related to metabolism and ion maintenance. Furthermore, we collaborate with partners at Cincinnati Children's to study how glioma forms in patients with neurofibromatosis.

Patients with NF1 mutations often have areas of hyperpigmentation, peripheral nerve sheath tumours and optic gliomas. Our fish models of NF1 frequently reproduce these manifestations (above).

Undergraduate Research

At Miami University we encourage undergraduates to participate in active research. Our lab is often looking for young talented undergraduates to assist in our research and develop essential biological lab techniques. If you are interested in performing research in the C-P lab fill out the form below to be added to our review list!

Publications

Charlton-Perkins MA, Cook TA, Friedrich M . Semper's Cells in the Insect Compound Eye: Insights into Ocular Form and Function (2021). Developmental Biology S0012-1606 (21)00178-0. doi: 10.1016/j.ydbio.2021.07.015

Charlton-Perkins M, Almeida AD, MacDonald RB, Harris WA. Genetic control of cellular morphogenesis in Müller glia (2019). GLIA 67(7): 1401-1411. doi: 10.1002/glia.23615.

MacDonald RB, Charlton-Perkins M, Harris WA. Mechanisms of Müller glial cell morphogenesis (2017). Current Opinions in Neurobiology 47:31-37. doi: 10.1016/j.conb.2017.08.005

Charlton-Perkins MA, Sendler ED, Buschbeck EK, Cook TA. Multifunctional glial support by Semper cells in the Drosophila retina (2017). PLoS Genetics 31;13(5). doi: 10.1371/journal.pgen.1006782.

Eldred MK, Charlton-Perkins M, Muresan L, Harris WA. Self-organising aggregates of zebrafish retinal cells for investigating mechanisms of neural lamination (2017). Development 144(6):1097-1106. doi: 10.1242/dev.142760.

Stahl AL, Charlton-Perkins M, Buschbeck EK, Cook TA. The cuticular nature of corneal lenses in Drosophila melanogaster (2017). Development Genes and Evolution 227(4):271-278. doi: 10.1007/s00427-017-0582-7.

Luebbering N, Charlton-Perkins M, Kumar JP, Rollmann SM, Cook T, Cleghon V (2013). Drosophila Dyrk2 plays a role in the development of the visual system. PLoS One 11,8(10). doi: 10.1371/journal.pone.0076775.

Jukam D, Xie B, Rister J, Terrell D, Charlton-Perkins M, Pistillo D, Gebelein B, Desplan C, Cook T (2013). Opposite feedbacks in the Hippo pathway for growth control and neural fate. Science Oct 11;342. doi: 10.1126/science.1238016.

Charlton-Perkins, M., Brown, N.L., and Cook, T.A (2011a). The lens in focus: a comparison of lens development in Drosophila and vertebrates. Molecular Genetics and Genomics 286, 189-213. doi: 10.1007/s00438-011-0643-y.

Charlton-Perkins, M., Whitaker, S.L., Fei, Y., Xie, B., Li-Kroeger, D., Gebelein, B., and Cook, T (2011b). Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling. Neural Development 6, 20. doi: 10.1186/1749-8104-6-20.

McDonald, E.C., Xie, B., Workman, M., Charlton-Perkins, M., Terrell, D.A., Reischl, J., Wimmer,E.A., Gebelein, B.A., and Cook, T.A (2010). Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events. Developmental Biology 347, 122-132. doi: 10.1186/1749-8104-6-20.

Charlton-Perkins, M., and Cook, T.A (2010). Building a fly eye: terminal differentiation events of the retina, corneal lens, and pigmented epithelia. Current Topics in Developmental Biology 93,129-173. doi: 10.1016/B978-0-12-385044-7.00005-9.

Xie, B., Charlton-Perkins, M., McDonald, E., Gebelein, B., and Cook, T (2007). Senseless functions as a molecular switch for color photoreceptor differentiation in Drosophila. Development 134, 4243-4253. doi: 10.1016/j.ydbio.2010.08.016.

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