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Molecular control of neurogenesis

We study the molecular mechanisms that control determination and proliferation of neural stem cells, their differentiation into functional neurons and their deregulation in brain cancer.

In the process of brain development over 1000 different types of neurons are generated from an initially homogeneous stem cell population. At which level is this diversity 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.

Drosophila suzukii assesses the quality of a ripe cherry before deciding where to lay an egg

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Annalisa Fico
Tenured researcher, CNR, IGB, Naples, Italy
Stephane Bugeon
Postdoc, UCL, London, UK
Antoine de Chevigny
Tenured Researcher, INMED, Marseille, France
Jean-Claude Platel
Tenured Researcher, INMED, Marseille, France
Camille Boutin
Tenured Researcher, INMED, Marseille, France

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Molecular control of neurogenesis

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 group 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 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? We developed an innovative in vivo model for glioma development in mice to study the role of signaling pathways and the precise role of microRNAs in cancer.

How are new neurons integrated in the postnatal and adult brain and what is 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 permanent growths. We investigate the role of this “ongoing development” and analyze the contribution of the different neuronal subtypes to odor perception and computing.