Research Groups

Portrait Caghan Kizll

Caghan Kizil

Molecular mechanisms of stem cell plasticity and regenerative neurogenesis in adult zebrafish brain

Previous and Current Research

The brains of aging humans are prone to neurodegenerative disorders and we are unable to counteract neuronal loss by regenerating lost cells. Patients with neurodegenerative conditions progressively loose neurons yet cannot form new neurons that would replace the lost ones. However, in nature, several vertebrates such as zebrafish bear a widespread regenerative ability that includes replenishment of neurons in the adult central nervous system due to the neurogenic activity of the progenitor cells. We have recently identified that this regenerative ability in fish requires turning on special molecular programs of the neural progenitor cells that in the end make regenerative neurogenesis possible. These findings suggest that regenerating organisms such as zebrafish could use special molecular programs to modulate the plasticity of the neural stem cells and enable restoration of compromised neural tissues. Hypothetically, these programs might also underlie the disparity between the regenerative capacities of zebrafish brain and mammalian brains. Therefore, we might consider neurodegenerative diseases of humans to some degree also as “stem cell diseases”. The main motivation for my independent research group will be to understand what it takes in terms of molecular programs for zebrafish brain to regenerate itself after neurodegeneration, and which parts of those relevant molecular programs are missing in mammalian brains. These findings will be important in terms of contributing to the efforts to design therapeutic approaches to circumvent the detrimental consequences of neurodegeneration in human brains and open up new avenues for regenerative medicine.

Caghan Kizil research: figure
Fig.: Various stimulations are affecting the physiological behaviour of neural stem/progenitor cells. The heart of the regenerative capacity thereof might lie in the ability of regenerating organisms to turn on special molecular programs that enable subsequent rebuilding lost tissues and cell types. For instance in zebrafish brain, acute neuronal loss induces radial glial cells (RGCs) to enhance their proliferation levels and form neurons that integrate into the existing circuitry and populate the lesion sites. My aim is to understand the special regenerative mechanisms partaking in neuronal restoration upon various modes of damage in adult zebrafish brain, especially after chronic neurodegeneration. The information gained from zebrafish bear the potential to be harnessed for inducing regenerative neurogenesis to a greater degree in human brains.
Future Projects and Goals
  • To learn from zebrafish how to enable the adult brains to better cope with neurodegenerative disease and regenerate
  • To identify the molecular mechanisms of neural stem cell plasticity in adult zebrafish brain after various types of tissue damage or physiological stimulations
Methodological and Technical Expertise
  • Zebrafish genetics
  • Cerebroventricular microinjection (CVMI)
  • Gene expression profiling and functional analyses
  • Immunohistochemical detection and microscopy
Selected Publications

Tincer, G., Mashkaryan, V., Bhattarai, P., Kizil, C.
Neural stem/progenitor cells in Alzheimer’s disease.
The Yale Journal of Biology and Medicine, 89(1), 23–35. (2016)

Kizil C, Küchler B, Yan JJ, Ozhan G, Moro E, Argenton F, Brand M, Weidinger G, Antos CL.
Simplet/Fam53b is required for Wnt signal transduction by regulating β-catenin nuclear localization.
Development. 141(18):3529–39. (2014)

Kizil C, Kyritsis N, Dudczig S, Kroehne V, Freudenreich D, Kaslin J, Brand M.
Regenerative neurogenesis from neural progenitor cells requires injury-induced expression of Gata3.
Developmental Cell, 23(6):1230–7 (2012)

Kyritsis N, Kizil C, Zocher S, Kroehne V, Kaslin J, Freudenreich D, Iltzsche A, Brand M.
Acute Inflammation Initiates the Regenerative Response in the Adult Zebrafish Brain.
Science, 338(6112):1353–6 (2012)

Kizil C, Dudczig S, Kyritsis N, Machate A, Blaesche J, Kroehne V, Brand M.
The chemokine receptor cxcr5 regulates the regenerative neurogenesis response in the adult zebrafish brain.
Neural Development 7:27 (2012)

CV

since 2014
Helmholtz Young Investigator Group Leader, German Center for Neurodegenerative Diseases (DZNE) Dresden within Helmholtz Association and joint appointment DFG-Center for Regenerative Therapies Dresden (CRTD), TU Dresden

2009–2014
Post-doctoral fellow, DFG-Center for Regenerative Therapies Dresden (CRTD), TU Dresden

2005–2009
Ph.D., Max Planck Institute for Developmental Biology, Tübingen

2003–2005
M.Sc., Max Planck Research School for Molecular Biology, University of Göttingen

1999–2003
B.Sc., Middle East Technical University, Ankara, Turkey

Contact

Center for Regenerative Therapies Dresden (CRTD)
TU Dresden
Fetscherstraße 105
Dresden, Germany

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