Institut für Humangenetik

Dissecting the dynamics of epigenetic transcriptional remodelling during neuronal development and age-associated neurodegeneration

Shaping excitatory responses of pyramidal neurons by the very diverse group of GABAergic interneurons is crucial for cortical information processing. Developmental defects that impair the establishment of such cortical circuits, have been implicated in a wide range of neurological disorders. Further, the selective vulnerability of inhibitory interneurons upon aging contributes to cognitive, sensory and motor performances of elderly.

Our research is focussed on the dynamics of epigenetic transcriptional control during neuronal development, function and age-associated neurodegeneration of the cerebral cortex. By dissecting interactive networks directing key events of these processes the pathophysiology of associated diseases can be better understood. Our work is based on the systemic and functional analysis of transgenic mouse models and diverse cell culture systems. For the cellular and sub-cellular analysis, we apply a battery of of biochemical, molecular and cell biological methods. These include primary neuronal cultures, functional in vitro assays, ex-vivo and in vivo genetic manipulations, methylation studies and life cell imaging. A recently established methodological focus relies on single cell and tissue-based global transcriptome analysis.


Figure 1

Figure 1: Schematic workflow of the experimental design for single cell transcriptome analysis. Embryonic tissue from MGE and POA neurogenic domains of the devleoping mouse telencephalon was used either directly for RNA isolation or as single cell preparations and subjected to global reverse transcription and amplification to generate global transcriptome cDNA libraries. NanoString was applied to validate the cDNA synthesis and amplification procedure regarding transcript representation and to profile transcriptomes of neuronal subtypes. MGE=medial ganglionic eminence. POA=preoptic area.



Pensold D, Symmank J, Hahn A, Lingner T, Salinas-Riester G, Donnie B, Ludewig F, Rotzsch A, Haag N, Andreas N, Schubert K, Hübner C, Pieler T and Zimmer G. The DNA Methyltransferase 1 (DNMT1) Controls the Shape and Dynamics of Migrating POA- Derived Interneurons Fated for the Murine Cerebral Cortex. Cerebral Cortex. online 2016 Nov; 1-19.

Gerstmann K, Pensold D, Symmank J, Khundadze M, Hübner Ch, Bolz J and Zimmer G. Thalamic afferents influence cortical progenitors via ephrinA5/EphA4 interactions. Development. 2015 Jan 1;142(1):140-50.

Zimmer G, Rudolph J, Landmann J, Gerstmann K, Steinecke A, Gampe C and Bolz J (2011) Bidirectional ephrinB3/EphA4 signaling mediates the segregation of MGE‑and POA derived interneurons in the deep and superficial migratory stream. J Neurosci: 31(50):18364-18380

Zimmer G, Schanuel SM, Burger S, Weth F, Steinecke A, Bolz J, Lent R (2010) Chondroitin Sulfate Acts in Concert with Semaphorin 3A to Guide Tangential Migration of Cortical Interneurons in the Ventral Telencephalon. Cerebral Cortex (10):2411-22

Zimmer G, Garcez P, Rudolph J, Niehage R, Weth F, Lent R, Bolz J (2008) Ephrin-A5 acts as a repulsive cue for migrating cortical interneurons. Eur J Neurosci 28:62-73.

Zimmer G, Kastner B, Weth F, Bolz J (2007) Multiple effects of ephrin-A5 on cortical neurons are mediated by SRC family kinasesJ Neurosci 27:5643-5653.





Else-Kröner Fresenius Stiftung


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Prof. Dr. Christian Hübner