Molecular control of neurogenesis
Group leader : H. Cremer
We study the genes and molecular mechanisms that control determination and proliferation of neural stem cells and their differentiation into functional neurons.
In the process of brain development over 1000 different types of neurons are generated from initially homogeneous stem cell population.
At which level this diversity is encoded? How is the proliferation of stem cells controlled to generate the correct number of neurons? What happens when proliferation control goes wrong and brain cancer develops? How do neurons integrate into the circuitry and what is their specific function?
We use the ongoing neurogenesis that occurs in the postnatal mammalian brain to address these questions and identify the signals and molecular cascades that control specific steps in neuron production. A particular focus of our work is set on the role of RNAs that do not encode proteins, but have regulatory functions to provide the stability and flexibility that is needed to generate and maintain a functional brain.
In mammals, including humans, neurogenesis is not limited to embryonic stages but is maintained in specific regions of the postnatal and adult brain. For example, in the forebrain neural stem cells along the ventricles keep generating throughout life new neuronal precursors that migrate into the olfactory bulb where they are added to the circuitry as interneurons that use GABA, dopamine and glutamate as their neurotransmitters. This process, resembling ongoing neural development, presents all crucial steps that are also seen in the embryo. However, as the process occurs ex-utero it is highly amenable to experimental manipulation, like in vivo electroporation, lineage tracing, and manipulation by chemo- and optogenetics. In addition, consequences of these changes can be easily observed by classical microscopy or by multi-photon in vivo microscopy.
In our lab we use this experimental model to investigate how neuron production and integration are controlled at the molecular and physiological levels, both in the normal and the diseased brain.
Specifically, we ask:
How is the stem cell compartment regionalized to produce different types of neurons? What are the mechanisms that generate this diversity in first place and maintain it throughout the animal’s life?
We found that cross regulatory interactions between transcription factors underlie this diversity and use new technologies to provide insight into their expression and function.
What is the role of non-coding RNAs in the process of neurogenesis?
We found that stem cell regionalization and proliferation is fine-tuned in an interplay between microRNAs and long non-coding RNAs. We develop new tools and strategies to investigate these interactions in the living brain.
What happens when proliferation and differentiation of new neurons gets out of control and cancer develops? What is the function of non-coding RNAs in cancer induction and progression?
To address this question, we study the role of different signaling pathways in the development of glioma and use innovative experimental strategies to identify the precise role of microRNAs in cancer.
How are new neurons are integrated in the postnatal and adult brain and how they achieve their specific function?
Using in vivo multiphoton imaging we found that olfactory bulb neurogenesis is not a replacement process, as has been thought so far, but that new neurons are constantly added to the structure, leading to significant growths. We investigate the role of this “ongoing development” and analyze the contribution of the different neuronal subtypes to odor perception and computing.
August 7th, 2020
Stem cell regionalization during olfactory bulb neurogenesis depends on regulatory interactions between Vax1 and Pax6
July 11th, 2019
Neuronal integration in the adult mouse olfactory bulb is a non-selective addition process.
November 1st, 2017
Direct and efficient transfection of mouse neural stem cells and mature neurons by in vivo mRNA electroporation
September 29th, 2017
Zic-proteins are repressors of dopaminergic forebrain fate in mice and C. elegans.
October 21st, 2016
miR-200 family controls late steps of postnatal forebrain neurogenesis via Zeb2 inhibition
June 7th, 2016
LAMP5 Fine-Tunes GABAergic Synaptic Transmission in Defined Circuits of the Mouse Brain.
June 17th, 2014
Reducing Glypican-4 in ES Cells Improves Recovery in a Rat Model of Parkinson's Disease by Increasing the Production of Dopaminergic Neurons and Decreasing Teratoma Formation.
June 14th, 2012
miR-7a regulation of Pax6 controls spatial origin of forebrain dopaminergic neurons
March 14th, 2012
Agrin-signaling is necessary for the integration of newly generated neurons in the adult olfactory bulb
January 19th, 2010
NeuroD1 induces terminal neuronal differentiation in olfactory neurogenesis.
February 28th, 2013
[Micro-RNA miR-7a controls the production of dopaminergic neurons in the mouse forebrain].
February 13th, 2013
Efficient neuronal in vitro and in vivo differentiation after immunomagnetic purification of mESC derived neuronal precursors.
November 21st, 2012
Plexin-B2 regulates the proliferation and migration of neuroblasts in the postnatal and adult subventricular zone.
January 5th, 2012
Dynamic expression of the pro-dopaminergic transcription factors Pax6 and Dlx2 during postnatal olfactory bulb neurogenesis.
April 13th, 2011
Targeted electroporation of defined lateral ventricular walls: a novel and rapid method to study fate specification during postnatal forebrain neurogenesis.
September 29th, 2010
The SRC homology 2 domain protein Shep1 plays an important role in the penetration of olfactory sensory axons into the forebrain.
June 5th, 2010
Expression and function of CXCR7 in the mouse forebrain.
April 1st, 2010
Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia.
November 1st, 2008
Gene expression analysis defines differences between region-specific GABAergic neurons.
June 1st, 2008
CXCL12/CXCR4 signalling in neuronal cell migration.
April 2nd, 2008
Efficient in vivo electroporation of the postnatal rodent forebrain.
December 20th, 2006
Molecular interaction between projection neuron precursors and invading interneurons via stromal-derived factor 1 (CXCL12)/CXCR4 signaling in the cortical subventricular zone/intermediate zone.
May 1st, 2006
Glial conversion of SVZ-derived committed neuronal precursors after ectopic grafting into the adult brain.
December 1st, 2004
Dynamics of Cux2 expression suggests that an early pool of SVZ precursors is fated to become upper cortical layer neurons.
April 1st, 2004
Purification of neuronal precursors from the adult mouse brain: comprehensive gene expression analysis provides new insights into the control of cell migration, differentiation, and homeostasis.
October 1st, 2002