Startseite

Herzlich Willkommen auf den Internetseiten der Experimentellen Embryologie des Anatomischen Instituts Tübingen.

Die Experimentelle Embryologie und Tissue Engineering

PD Dr. Andrea Wizenmann

Normal function of the nervous system requires that neurons are precisely wired together. The diverse functions in the central nervous system – from cognition to movement -  depend on orderly neuronal networks.. These arise during embryonic development, though the precise control of proliferation and gene expression. Understanding these mechanisms is an important first step in understanding the formation of the nervous system. Development also delivers vital insights into the origin, prevention and treatment of nervous system disorders that range from neurological and psychiatric syndromes to neural tumours.
We are interested in the development of the midbrain (mesencephalon)– a part of the brain involved in coordinating sensory inputs and motor outputs in regulating complex reflexes such as eye movement. The midbrain also contains dopaminergic neurones of the the substantia nigra, which are selectively lost in Parkinson’s disease. The lab focuses on the mechanisms and molecules, which regulate the different patterns of proliferation and differentiation in ventral and dorsal midbrain regions. In particular, we study the influence of different factors (transcription factors, signalling proteins and micro RNAs) on cell proliferation and gene expression and try to work out if and when yes how these factors regulate each other. Tissue transplantation, protein overexpression or knock down together with molecular techniques are combined to study these questions.

Pattern of neuronal differentiation and axon trajectories in the early midbrain

Neurones were labelled with a neurofilament antibody. All 4 pictures show ‘open book’ preparations ofdi - and mesencephalon, whereby the ventral midbrain stays left and right of the floor plate (FP) and the dorsal midbrain is separated at the roof plate (RP). At stage 14, only few neurones have developed in the dorsal midbrain (MTN neurones) and posterior diencephalon (INC). At stage 15, many neurones have developed axons, which grow ventrally (MTN) or posteriorly (ICN). At stage 16 and 17 the axons of MTN and ICN assemble to pioneer the tract of the MLF and LLF, respectively.

Abbreviations: DE - diencephalon, FP - floor plate, INC- interstitial nucleus of Cajal, ME - mesencephalon, LLF - lateral longitudinal fascicle, MLF -medial longitudinal fascicle, MTN - mesencephalic trigeminal nucleus, RE - rhombencephalon, RP - roof plate, R1 - rhombomere 1.  Scale bars: 100µm.

Publications

Sirko, S., Holst, A.v., Wizenmann, A., Weber, A., Theocharidis, U., Götz, M., and Faissner, A. (2010) Chondroitin Sulfates are required for FGF-2 dependent proliferation and maintenance in neural stem cells and for EGF dependent migration of their progeny.
Stem Cells 28(4):775-87.

Hirschberg A, Deng S, Korostylev A, Paldy E, Costa MR, Worzfeld T, Vodrazka P, Wizenmann A, Götz M, Offermanns S, Kuner R. (2010) Gene deletion mutants reveal a role for semaphorin receptors of the Plexin-B family in mechanisms underlying corticogenesis.
Mol Cell Biol. 2010 Feb;30(3):764-80.

Wizenmann, A., Sonnier, L., Brunet, I., Lam, J., Zarbalis, K., Weisenhorn-Vogt, D., Weinl, C., Holt, C., Wurst, W., and Prochiantz,A.,. (2009) Retinal ganglion cell axon guidance by extracellular Engrailed.
Neuron 64(3):355-66

Chittka, A., S., Volff, J-N. Wizenmann A.C. (2009) Identification of Genes differentially expressed in the dorsal and ventral chick midbrain.
BMC Dev. Biol. 9 (29)

Leucht,C., Wizenmann, A., Christian Stigloher,C., Ruth Klafke, R., Folchert, A, and Bally-Cuif, L. (2008) Concerted regulation of Fgf signaling and neurogenesis by a single microRNA in the midbrain-hindbrain domain of the vertebrate neural tube. Nature Neuroscience 11 (6): 641-648.

Li, N., Volff’ J-N., Wizenmann, A. (2007) Expression and function of Rab23 in the chick nervous system.
Dev.Dyn. 236 (11): 2993 – 3006.

Sirko, S., Holst, A.v., Wizenmann, A., Götz, M., and Faissner, A. (2007) Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentatiation and neurogenesis in neural stem/progenitor cells.
Development. 134(15):2727-38.

Holm, Pontus, C., Mader, M.T., Haubst, N., Wizenmann, A., Sigvardsson, M.,and Götz, M. (2007) Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon.
Mol Cell Neurosci. 34(1):99-119.

von Frowein, J., Wizenmann, A., and Götz, M. (2006) The transcription factors Emx1 and Emx2 suppress choroid plexus development and promote neuroepithelial cell fate.
Dev. Biol. 296(1):239-52.

Li N, Hornbruch, A., Klafke, R., Katzenberger, B., and Wizenmann A. (2005) Specification of Dorso-Ventral Polarity in the Embryonic Chick Mesencephalon and its Presumptive Role in Midbrain Morphogenesis.
Dev Dyn. 233(3):907-20.

Lutz, M., Kriegelstein, K., Wizenmann, A., ten Dijke, P. , Sebald, W., and Knaus, P. (2004) Nerve growth factor mediates activation of the Smad pathway in PC12 cells.
Eur J Biochem 271:920-931.

Molle, KD, Chedotal, A., Rao, Y., Lumsden, A., Wizenmann A. (2004) Local inhibition guides the trajectory of early longitudinal tracts in the developing chick brain.
Mech Dev 121:143-156.

Wizenmann, A. (2003) Prinzipien der Musterbildung im Gehirn.  Bioforum 1.

Eickholt B., Graham, A., Lumsden, A., and  Wizenmann, A. (2001).  Rhombomere interactions control the segmental differentiation of hindbrain neurons.
MCN 18, 141-148.

Jungbluth, S., Larsen, C., Wizenmann, A., and Lumsden, A. (2001). Cell mixing between the embryonic midbrain and hindbrain.
Curr Biol 11, 204-7.

Wizenmann, A. and Bahr, M. (1998). Growth preferences of adult rat retinal ganglion cell axons in retinotectal cocultures.
Journal of Neurobiology 35, 379-387.

Wizenmann, A. and Lumsden, A. (1997). Segregation of Rhombomeres by Differential Chemoaffinity.
Mol Cell Neurosci 9, 448-59.

Wizenmann, A. and Bahr, M. (1997). Growth characteristics of ganglion cell axons in the developing and regenerating retino-tectal projection of the rat.
Cell Tissue Res 290, 395-403.

Bahr, M. and Wizenmann, A. (1996). Retinal ganglion cell axons recognize specific guidance cues present in the deafferented adult rat superior colliculus.
J Neurosci 16, 5106-16.

Logan, C*., Wizenmann, A.*, Drescher, U., Monschau, B., Bonhoeffer, F. and Lumsden, A. (1996). Rostral optic tectum acquires caudal characteristics following ectopic engrailed expression.
Curr Biol 6, 1006-14.
*both authors contributed equally to the work

Gotz, M., Wizenmann, A., Reinhardt, S., Lumsden, A. and Price, J. (1996). Selective adhesion of cells from different telencephalic regions.
Neuron 16, 551-64.

Wizenmann, A., Thanos, S., von Boxberg, Y. and Bonhoeffer, F. (1993a). Differential reaction of crossing and non-crossing rat retinal axons on cell membrane preparations from the chiasm midline: an in vitro study.
Development 117, 725-35.

Wizenmann, A., Thies, E., Klostermann, S., Bonhoeffer, F. and Bahr, M. (1993b). Appearance of target-specific guidance information for regenerating axons after CNS lesions.
Neuron 11, 975-83.

Bahr, M., Wizenmann, A. and Thanos, S. (1992). Effect of bilateral tectum lesions on retinal ganglion cell morphology in rats.
J Comp Neurol 320, 370-80.

Wizenmann, A. and Thanos, S. (1990). The developing chick isthmo-optic nucleus forms a transient efferent projection to the optic tectum.
Neurosci Lett 113, 241-6.