Prof. Dr. Klaus Unsicker
Department of Molecular Embryology
Institute of Anatomy and Cell Biology
Tel: 0761 / 203 5193
Website: Prof. Dr. Klaus Unsicker
Growth factors in development and functions of the nervous system
The Unsicker lab studies aspects of neural development, functions, and disease, addressing both molecular-cellular and systems issues. We focus on the development of neural crest (NC) derivatives, functions of limbic areas, and meso-striatal / meso-limibic systems in health and disease. We have a long-standing interest in the roles of select members of the transforming growth factor-ßs (TGF-ßs), fibroblast growth factors (FGFs), and neurotrophins.
An important topic in the research of the laboratory is the molecular understanding of neuronal survival and death. Methodologies include generation and analysis of mouse mutants, cell and tissue culture, biochemistry, molecular biology, histology, and electrophysiology. Several projects of the group are described below.
Current projects include
The NC gives rise to different types of neurons, glial, endocrine, and mesenchymal cells and, hence, is an excellent model for exploring mechanisms underlying the generation of cell diversity. We focus on the development of sympathetic neurons and neuroendocrine chromaffin cells. Whether these cells are derived from one common lineage, the SA cell lineage, or from two distinct lineages has been an open issue until very recently. In a joint effort with the Kalcheim lab (Hebrew University Jerusalem) we have performed single cell electroporations of GFP-encoding plasmid into delaminating NC cells in chick embryos and followed their subsequent migration into the target organs, i.e. sympathetic ganglia and adrenal gland, respectively. In the large majority of cases the progeny of GFP-expressing cells was detected in both sympathetic ganglia and adrenal glands suggesting that the cells share a common progenitor at the level of the neural tube . In previous studies we have shown that, contrary to a classic hypothesis, glucocorticoid hormones and the adrenal cortex are not required for most aspects of chromaffin cell differentiation [2,3]. Furthermore, we have analyzed, inter alia, the transcription factor network underlying chromaffin cell development [e.g. 4,8] and the role of BMP-4 for chromaffin cell fate determination and differentiation [5; cf. figure].
Furthermore, in a collaboration with the Schütz lab (DKFZ Heidelberg) we study the role of glucocorticoids for the maintenance of intra- and extra-adrenal chromaffin tissue [6,7] and the impact of autophagy on chromaffin cell survival. For a recent review, see . Current experiments, conducted in a collaboration with the Ernsberger, Rohrer (MPI Frankfurt) and Huber (Anatomy Freiburg) labs elucidate the role of microRNAs for sympathetic neuron and chromaffin cell development . Our final goal is to fully understand the mechanisms that generate the diversity of sympathetic neurons and chromaffin cells during migration of progenitors to the target regions.
E15 embryonic chick adrenal gland showing expression of BMP-4 mRNA (blue) and TH mRNA.
 Shtukmaster, S. et al. (2013) Neural Development 8:12 doi:10:1186/1749-8104-8-12
 Finotto, S. et al. (1999) Development 126, 2935-2944
 Gut, P. et al. (2005) Development 132, 4611-4619
 Huber, K. et al.. (2002) Development 129, 4729-4738
 Huber, K. et al. (2008) Neural Development 3, 28 doi :191186/1749-8104-3-28
 Parlato, R. et al. (2009) Endocrinology 150, 1775-1781
 Schober, A. et al. (2013) Neuroendocrinology 25, 34-47
 Unsicker, K. et al. (2013) Mech. Dev. 130: 324-329
 Stubbusch, J. et al. (2013) Neural Development 8: 16
 Stubbusch, J. et al. (2015) Dev. Biol. 400:210-233
GDF-15 is a novel distant member of the TGF-ßs, originally identified in our laboratory as a potent trophic factor for midbrain dopaminergic neurons, the neuron population predominantly affected in Parkinson's disease . We have generated a GDF-15 knockout mouse, which shows progressive postnatal motoneuron loss and dysmyelination in peripheral nerves .
GDF-15 also seems to be involved in the generation and differentiation of neural stem cells. (in collaboration with the Ciccolini lab, IZN Heidelberg, and the von Bohlen lab, Greifswald). Despite its potency as a neurotrophic factor, when applied to CNS  and PNS lesion paradigms , analysis of GDF-15 knockout mice has revealed that endogenous GDF-15 implies no benefit to CNS neurons following lesion [4,5]. For a recent review, see .
 Strelau, J. et al. (2000) J. Neuroscience 20: 8597-8603
 Strelau, J. et al. (2009) J. Neuroscience 29: 13640-13648
 Carrillo-Garcia, C. et. al. (20149 Development 141.773-783
 Mensching, L. et al. (2012) Cell Tiss Res. 350: 225-238
 Charalambous, P. et al. (2013) Cell Tiss Res. 353: 1-8
 Wang, X. et al. (2015) Cell Tiss. Res. 362:317-330
 Machado, V. et al.(2016) Neurobiol. Dis. 88:1-15
 Unsicker, K. et al. (2013) Cytokine Growth Factor Rev. 24: 373-384
New neurons in dentate gyrus labeled with doublecortin
The neurotrophins (BDNF) and neurotrophin-3, as well as their receptors trkB and trkC, respectively, are widely expressed in the nervous system and serve important functions during development. In a collaboration with the von Bohlen lab, Greifswald, we have found that aged mice, which are heterozygous null for trkB and trkC, show pronounced losses of midbrain dopaminergic neurons, including accumulations of α-synuclein (red in figure below), a hallmark of Parkinson´s disease .
Analyses of mice with partial or regionally specific complete deficits in trkB expression have revealed specific reductions and morphological alterations in dendritic spines (see figure below), essential structures in synaptic signalling and the determination of behaviour .
In collaborations with the von Bohlen, Grass, and Hempstead laboratories we have revisited roles of the neurotrophin receptor p7 fo hippocampal structure and cholinergic system [cf. 3,4].
 Bohlen und Halbach, O.v, et al. (2005) FASEB J. 19: 1740-1742
 Bohlen und Halbach, O.v., et al. (2006) Biol. Psychiatry 59: 793-800
 Egorov, A.V. et al. (2006) Eur. J. Neuroscience 24: 3183-3194
 Dokter, M. et al. (2015) Brain Struct. Funct. 220:1449-1462
 Poser, R. et al. (2015) Front. Neuroanat. 9:63
 Imrady, K. et al. (2014) j. Neuroscience 34:3419-3428
The laboratory has made seminal contributions to elucidating functions of FGFs (with a focus on FGF-2) in the nervous system. These include, inter alia, promotion of survival of select developing and lesioned neuron populations in the central and peripheral nervous system [1,2]. Using FGF-2- and FGF receptor-deficient mice we study the physiological relevance of FGF signalling for midbrain dopaminergic and cortical neurons [4, 9], FGF-dependent regulation of astroglia differentiation [3, 5, 8], neural progenitor cells in the dentate gyrus ,and the role of FGFs in animal models of major depression  (in collaborations with the von Bohlen lab, Greifswald, the Gass lab, ZI Mannheim, and the Ek and Saunders labs, Gothenburg, Melbourne).
 Unsicker, K., et al. (1987) Proc. Natl. Acad. Science USA 84, 5459-5463
 Otto, D. & Unsicker, K (1990) J. Neuroscience 10, 1912-1921
 Reuss, B., et al. (2003) J. Neuroscience 23, 6404-6412
 Zechel, S., et al. (2006) Eur. J. Neuroscience 23, 1671-1675
 Irmady, K. & Unsicker, K. (2011) Glia 59: 708-719
 Jarosik, J. et al. (2011) Restor. Neurol. Neurosci. 29: 153-165
 Werner, S. et. al. (2011) J. Neurosci. Res. 89: 1605-1617
 Saunders, N.R. et al. (2016) Dev. Neurobiol. in press
 Baum, P. et al. (2016) Intl. J. Dev. Neuroscience, in press
Dr. Stella Shtukmaster