Mark VanBerkum (ad5089)

Biological Sciences, Neuroscience

Biological Sciences Bldg, Suite 5178

• Developmental neurobiology

Directional movement of the growth cone, the terminal extension of the outgrowing axon, is a complex signal transduction process dictated by a series of attractive and repulsive guidance cues lining the path. Cell surface receptors detect these cues and initiate intracellular signaling events to dictate axon outgrowth and steering. We seek to understand this signaling process by studying an axon’s decision to cross or not to cross the midline of an embryo using the molecular, cellular and genetic toolbox of Drosophila.

The ventral cord of a Drosophila embryo is a ladder-like scaffold of axons with an anterior (AP) and posterior (PC) commissure joining longitudinal connectives (LC) on each side of the midline. Netrins are chemoattractive cues guiding axons across the midline. Netrins are detected by Frazzled, which in turn activates several intracellular signaling pathways to regulate axon outgrowth. One signaling molecule appears to be Abelson Tyrosine Kinase, a major regulator of actin dynamics. We are seeking to understand how Frazzled and Abelson cooperate to guide axons across the midline. This project utilizes biochemical and cellular techniques to understand how Frazzled and Abelson physically interact, while genetic manipulations help us understand how they work in vivo to establish axon connections.

A second project examines the role of Adhesion G-Protein coupled receptors (GPCRs) in the formation of the embryonic nerve cord. GPCRs are familiar receptors for hormones and neurotransmitters that activate trimeric G-proteins. The growing family of Adhesion GPCRs is thought to activate G-proteins in response to adhesive conditions dictated by their extracellular domains. We are using the Drosophila genetic toolbox to begin testing whether these receptors might play a role in the development of the nerve cord.

• Wayne State University research grant,1996-1997
• National Science Foundation, Signal Transduction Mechanisms Regulating Axon Guidance of Drosophila Pioneer Neurons. (#9604622) Feb. 1997-Jan. 2001, $260,116
• Whitehall Foundation, Inc., Elucidating the Ca2+-Calmodulin Signaling Pathway used During Axon Guidance. Mar. 1997-Dec. 2000, $90,000
• National Science Foundation, Multi-User Instrumentation Proposal: A Laser Confocal Microscope for Biological Imagining. (#70099) (Co-PI with Friedrich, Elferink, Lilien, and Popadic), $200,000
• National Multiple Sclerosis Society, Pilot Grant: Using Drosophila Genetics to Understand Neural-Glia Interactions in MS. Sept., 2000 $25,000, one-year. (John Kamholz, CMMG is co-PI)
• Wayne State University Research Grant, summer 2001
• National Science Foundation, Intracellular Signaling During Midline Guidance in Drosophila. (#91478) June 15, 2001 – June, 2004, $313,127 (plus 6 month no-cost extension)
• National Science Foundation, "Regulating Myosin Activity During Midline Guidance in Drosophila," (#0416472) 2/2005-2/2009, ~$450,000
• WSU-Bridge Fund 5/09-9/10, $35,000
• NIH- NICHD – R03: 1R03HD058691-01A21, G-protein Coupled Receptors and Axon Guidance in the Drosophila Embryonic Nerve Cord. Priority score released 3/4/09 was 13 (2%). Notice of Award received 3/23/2010 for start date of April 1, 2010. ~$150,000
• National Science Foundation, Award #IOS-1121025, Frazzled and Abelson Tyrosine Kinase Interact to Regulate Midline Guidance, Aug. 15, 2011 - July 13, 2015, $508,310

• Fritz, J. L. and VanBerkum, M. F. A. (2000) Calmodulin and Son-of-Sevenless Dependent Signaling Pathways Regulate Midline Crossing of Axons in the Drosophila CNS. Development 127:1991-2000
• Kim, Y.S., Furman*, S., Sink, H. and VanBerkum, M. F. A. (2000) Calmodulin and Profilin Co-Regulate Axon Outgrowth in Drosophila. J. Neurobiology 47:26-38
• Kim, Y.S., Fritz, J.L., Seneviratne, P.A., and VanBerkum, M.F.A. (2002) Constitutively Active Myosin Light Chain Kinase Alters Axon Guidance Decisions in Drosophila Embryos. Dev Biol 249,367-381
• Rhee, J., Mahfooz, N.S., Balsamo, J., Lilien, J., and VanBerkum, M.F.A. (2002) Roundabout Signals Regulate N-cadherin Mediated Adhesion. Nature Cell Biol. 4,798-805 [DOI: 10.1038/ncb858]
• Fritz, J.L. and VanBerkum, M.F.A. (2002) Rho Family GTPases Regulate Axon Guidance at the Midline of the Drosophila CNS. Dev. Biol. 252,46-58
• Hsouna, A., Kim, Y.S. and VanBerkum, M.F.A. (2003) Abelson Tyrosine Kinase is Required to Transduce Midline Repulsive Cues. J. Neurobiol 57, 15-30
• Balan, V. Miller, G.S. Balan, K., Chong, Z.Z., Li, F., Freeman, C., VanBerkum, M.F.A., Arking, R., Maiese, K., and Tzivion, G. (2008) Lifespan Extension and Neuronal Cell Protection by the Drosophila Nicotinamidase D-NAAM. J. Biol. Chem. J. Biol. Chem, 283(41):27810-9. Epub 2008 Aug 4
• Dorsten, J. N., Kolodziej, P. A., and Vanberkum, M. F. (2007). Frazzled regulation of myosin II activity in the Drosophila embryonic CNS. Dev Biol 308, 120-32
• Hsouna, and VanBerkum, M.F.A. (2008) Abelson Tyrosine Kinase and Calmodulin Interact Synergistically to Transduce Midline Guidance Cues In the Drosophila Embryonic CNS. Int J Dev Neurosci. 26; 345-354 [Epub ahead of print, Dec. 2007]
• Dorsten, J. N., and VanBerkum, M. F. (2008). Frazzled Cytoplasmic P-motifs are Differentially Required for Axon Pathway Formation in the Drosophila Embryonic CNS. Int J Dev Neurosci. 26(7):753-61. Epub 2008 Jul 11
• Dorsten, J.N., Varughese, B.E., Karma*, S.R., Seeger, M.A. and VanBerkum, M.F.A. (2010) Over-expression of Abelson Tyrosine Kinase in a frazzled mutant suppresses commissure formation. PLoS One 5(3):e9822. (on-line March 23, dx.plos.org/10.1371/journal.pone.0009822)
• Patel, MV, Hallal, DA, Jones*, JW1,2, Bronner*, DN1, Zein*, R., Caravas, J2, Husain, Z., Friedrich M, and Vanberkum MFA. Dramatic expansion and developmental expression diversification of the Methuselah gene family during recent Drosophila evolution. (2012). J Exp Zool B Mol Dev Evol. 2012 Jul;318(5):368-87. doi: 10.1002/jez.b.22453
• Meghna Patel, Mark FA VanBerkum, Jun-yi Zhu, Adam Richman, Zhiping Jiang, Zhe Han. (2016) Gia/Mthl5 is an aorta specific GPCR required for Drosophila heart tube morphology and normal pericardial cell positioning. Dev Biol. 414(1):100-7. doi: 10.1016/j.ydbio.2016.03.009
• Cheong, HSJ and VanBerkum, MFA. (2017) Long disordered regions of the C-terminal domain of Abelson tyrosine kinase have specific and additive functions in regulation and axon localization. PLoS One. 2017 Dec 12;12(12):e0189338. doi: 10.1371/journal.pone.0189338. eCollection 2017
• Han S.J. Cheong, Mark Nona, Samantha B. Guerra, Mark F.A. VanBerkum* The first quarter of the C-terminal domain of Abelson regulates the WAVE regulatory complex and Enabled in axon guidance. 2020 Neural Dev. 2020 May 2;15(1):7. doi: 10.1186/s13064-020-00144-8