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Gene regulatory mechanisms of neocortex evolution - Mareike Albert

Neocortex of a developing mouse embryo

The neocortex is considered to be the seat of higher cognitive functions in humans. During its evolution, most notably in humans, the neocortex has undergone considerable expansion, which is reflected by an increase in the number of neurons. Neocortical neurons are generated during development by neural stem and progenitor cells. Epigenetic mechanisms play a pivotal role in orchestrating the behavior of stem cells during development. We are interested in the mechanisms that regulate gene expression in neural stem cells, which have implications for our understanding of neocortex development and evolution, neural stem cell regulation and neurodevelopmental diseases.

Figure: Epigenome editing in neural progenitor cells of the developing neocortex. Progeny of electroporated cells express GFP (green) and nuclei are stained with DAPI (blue). Image by Nereo Kalebic.

Previous and current research

Epigenetic regulation of neocortex development

During the development of the mouse neocortex, stem and progenitor cells initially proliferate, then sequentially give rise to neurons destined to different cortical layers and finally switch to gliogenesis resulting in the generation of astrocytes and oligodendrocytes. Precise spatial and temporal regulation of neural progenitor differentiation is key for the proper formation of the complex structure of the neocortex. An impairment of the development of the brain, as observed in patients with neurodevelopmental disorders, is frequently linked to compromised intellectual abilities.

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Future projects and goals

The aims of our research are

  • to further develop in vivo epigenome editing tools to probe the role of histone modifications at specific loci during development
  • to understand how epigenetic mechanisms contribute to the precise regulation of neocortex development
  • to identify and characterize gene regulatory regions that may have contributed to human brain evolution
  • to investigate the role of non-coding genetic variants in neurodevelopmental diseases

Group leader

Selected publications

Albert M, Huttner WB (2018). Epigenetic and transcriptional pre-patterning - an emerging theme in cortical neurogenesis. Front Neurosci. doi: 10.3389/fnins.2018.00359.

Albert M, Kalebic N, Florio M, Lakshmanaperumal N, Haffner C, Brandl H, Henry I, Huttner WB (2017). Epigenome profiling and editing of neocortical progenitor cells during development. EMBO J. 36: 2642-2658.

Tardat M, Albert M, Kunzmann R, Liu Z, Kaustov L, Thierry R, Duan S, Brykczynska U, Arrowsmith CH, Peters AH (2015). Cbx2 targets PRC1 to constitutive heterochromatin in mouse zygotes in a parent-of-origin dependent manner. Mol Cell. 58(1): 157-71.

Florio M, Albert M, Taverna E, Namba T, Brandl H, Lewitus E, Haffner C, Sykes A, Wong FK, Peters J, Guhr E, Klemroth S, Prüfer K, Kelso J, Naumann R, Nüsslein I, Dahl A, Lachmann R, Pääbo S, Huttner WB (2015). Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science. 347(6229): 1465-70.

Albert M, Schmitz SU, Kooistra SM, Malatesta M, Morales Torres C, Rekling JC, Johansen JV, Abarrategui I, Helin K (2013). The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3. PLoS Genet. 9(4): e1003461.

Puschendorf M, Terranova R, Boutsma E, Mao X, Isono K, Brykczynska U, Kolb C, Otte AP, Koseki H, Orkin SH, van Lohuizen M, Peters AH (2008). PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. Nat Genet. 40(4): 411-20.

Group members

Contact

Group Leader

Dr. Mareike Albert

+49 (0)351 458 82312

Mareike.Albert[at]tu-dresden.de

Funding