Research - Institute of Genetics - Developmental Genetics Unit - Laboratory of Actin Cytoskeleton Regulation / MTA-SZBK-NAP-B Axon Growth and Regeneration Group

József MIHÁLY
scientific adviser

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Rita GOMBOS research associate
Szilárd SZIKORA research associate
Dávid FARKAS junior research associate
István FÖLDI research associate
Gabriella GAZSÓ- GERHÁT Ph.D. student
Krisztina TÓTH Ph.D. student
Péter KALTENECKER Ph.D. student
Anikó BERENTE laboratory assistant

DROSOPHILA DEVELOPMENTAL BIOLOGY

The highly dynamic actin cytoskeleton is one of the structurally and functionally most important cellular constituents. The actin cytoskeleton is involved in such fundamental cell biological processes as the maintenance of cell shape, cell division, intracellular transport, and motility. Furthermore, it is also well established that the actin cytoskeleton plays a central role in the growth and proper navigation of neuronal axons and dendrites necessary for the formation of a functional nervous system. Our major scientific interest is to gain a better understanding of the molecular mechanisms of axonal growth and guidance by uncovering the role of the growth cone actin cytoskeleton regulatory proteins.


The hallmarks of neurons are their slender cellular extensions which electrically wire the brain and ensure communication between the neurons themselves and other cell types of the body. It is well known that the formation and growth of these neuronal extensions relies critically on the actin-rich distal tip region or growth cone of the neurites. Although it is clear that the proper control of the dynamic actin rearrangements is essential for growth cone advance, the regulation of this process has so far remained poorly understood.

By using different Drosophila neuronal model systems, our group has recently provided compelling evidence that the formin proteins of the DAAM subfamily play a pivotal role during axonal growth regulation by promoting filopodia formation in the growth cone periphery. Moreover, we have collected several lines of evidences suggesting that the function of DAAM in developing neurons has been conserved during evolution. Recently, we have shown that DAAM acts in concert with the actin nucleator Arp2/3 complex to facilitate the formation of bundled actin filaments necessary for filopodia formation. Currently, we are undertaking genetic and biochemical approaches to identify the guidance cues and their signaling pathways that control directed axon growth by regulating the activity of DAAM and Arp2/3. Our main future goal is the comprehensive analysis of the regulatory systems acting through DAAM and Arp2/3 to gain a deeper insight into the molecular mechanism that powers the growth cone actin cytoskeleton during axonal growth.



The localization of dDAAM in the Drosophila embryonic CNS (B,C) and in growth cones of cultured neurons (E-F).

Considering that certain developmental disorders, accidental injuries, and neurodegenerative diseases often result in severe axonal growth defects or axonal injuries, our studies are of potential biomedical relevance as they may help to develop more efficient neuronal regeneration methods.

Selected publications

Dollar G, Gombos R, Barnett AA, Sanchez Hernandez D, Maung SM, Mihály J, Jenny A. Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila. Genetics 202 (3):1135-51 (2016).

Gombos R, Migh E, Antal O, Mukherjee A, Jenny A, Mihály J. The Formin DAAM Functions as Molecular Effector of the Planar Cell Polarity Pathway during Axonal Development in Drosophila. J Neurosci. 35(28):10154-67 (2015).

Molnár I, Migh E, Szikora S, Kalmár T, Végh AG, Deák F, Barkó S, Bugyi B, Orfanos Z, Kovács J, Juhász G, Váró G, Nyitrai M, Sparrow JC and Mihály J. DAAM is required for thin filament formation and sarcomerogenesis during muscle development in Drosophila. PLoS Genetics 10(2): e1004166 (2014)

Nelson KS, Khan Z, Molnár I, Mihály J, Kaschube M, Beitel GJ., Drosophila Src regulates anisotropic apical surface growth to control epithelial tube size. Nat Cell Biol. 14:518-525 (2012)

Goncalves-Pimentel C, Gombos R, Mihaly J, Sanchez-Soriano N, Prokop A. Dissecting Regulatory Networks of Filopodia Formation in a Drosophila Growth Cone Model. PLoS One 6(3):e18340 (2011)

Barko S, Bugyi B, Carlier MF, Gombos R, Matusek T, Mihaly J. and Nyitrai M. Characterization of the biochemical properties and biological function of the formin homology domains of Drosophila DAAM. J. Biol. Chem. 285: 13154-13169 (2010)

Matusek, T., Gombos, R., Szécsényi, A., Sánchez-Soriano, N., Czibula, A., Pataki, C., Gedai, A., Prokop, A., Raskó, I. and Mihály, J. (2008). Formin proteins of the DAAM subfamily play a role during axon growth. J. Neurosci. 28: 13310-13319.

Matusek, T., Djiane, A., Jankovics, F., Brunner, D., Mlodzik, M. and Mihály, J (2006). The Drosophila formin DAAM regulates the tracheal cuticle pattern through organizing the actin cytoskeleton. Development 133: 957-966.

Boutros, M., Mihaly, J., Bouwmeester, T. and Mlodzik, M (2000). Signaling specificity by Frizzled receptors in Drosophila. Science 288, 1825-1828.

Barges, S., Mihaly, J., Galloni, M., Hagstrom, K., Muller, M., Shanower, G., Schedl, P., Gyurkovics, H. and Karch, F (2000). The Fab-8 boundary defines the distal limit of the bithorax complex iab-7 domain and insulates iab-7 from initiation elements and a PRE in the adjacent iab-8 domain. Development 127, 779-790.