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Neurogenesis and circuit development

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Team leader: Jean Livet

  • Development of neural circuits Slide 1
  • Development of neural circuits Slide 2
  • Development of neural circuits Slide 3
  • Development of neural circuits Slide 4
  • Development of neural circuits Slide 5
  • Development of neural circuits Slide 6

 

Introduction

We study how the neural cells that compose brain and retinal circuits are generated, differentiate and interconnect during development using new genetic engineering and imaging approaches applicable to trace their connectivity and lineage.

Presentation

Information processing in the brain and retina relies on extraordinarily complex and precisely organized assemblies of neuronal and glial cells. The development of these networks raises two major questions: how are adequate numbers and types of their cellular components generated? How do these cells distribute in nervous tissue and interconnect together? Our group develops and applies new genetic engineering and imaging approaches to study these questions with cellular precision in intact neural tissue.


TeamBrainbow
To individually track neural cells in their native environment, we employ Brainbow, a transgenic strategy that distributes combinations of fluorescent proteins of distinct colors (red, yellow, cyan…) among cells of a tissue (Livet et al. Nature 2007). Brainbow color markers discriminate closely apposed cells, facilitating tracing of their processes in studies of neural circuitry. Based on Brainbow, we have developed an approach to trace the lineage of multiple individual neural stem cells simultaneously and identify their clonal progeny with color labels (Loulier et al. Neuron 2014). We also develop other synthetic biology methodologies with the aim of providing new information on the development of neural cells and circuits.

Neural stem cell potentialities and regulation
Neuronal and glial cells of the brain and retina are generated directly or indirectly by stem/progenitor cells located in the embryonic neuroepithelium. Understanding how these progenitors produce appropriate numbers and types of neural cells and how their progeny distributes within brain tissue is essential to link neural circuit development, structure and function and uncover the roots of neurodevelopmental disorders. We study these aspects in the embryonic cortex and retina using multicolor clonal analysis. Brainbow transgenes allow us to individually mark embryonic neural progenitor cells with distinct colors and identify their respective descent from embryonic to adult stages. We apply this scheme to define cortical and retinal progenitor output, understand their regulation and characterize the organization of their neuronal and glial descent in mature nervous tissue.

 

Sensory circuits structure and development
The fine-scale connectivity pattern of neural circuits reflects their developmental history and largely conditions their function. Dense mapping of connectivity with individual synapse resolution is therefore needed for comprehensive circuit analysis in normal and pathological conditions. To this aim, we apply Brainbow labeling for “connectomic” tracing of select sensory networks, with the aim of revealing new features of these circuits and shedding light on their assembly and remodeling during development.


Research areas

Neural stem cells fate and regulation: we use new cell lineage analysis approaches to characterize the potentialities of embryonic neural stem cells and assay their regulation.

Connectomics: we combine Brainbow genetic labeling with new optical imaging methodologies to study the fine-scale layout and development of specific sensory circuits.

Genetic engineering and synthetic biology: we develop genetic switches and transgenic reporter systems such as Brainbow to inform on the layout, interaction and developmental history of individual neural cells in their intact environment.


 

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Joining the lab

Interested candidates with a preferred expertise in neurodevelopment, genetic engineering and/or optical imaging are welcome to enquire for job possibilities.


Publications


Support

  • Inserm
    Inserm
  • CNRS
    CNRS
  • UPMC
    UPMC
  • ANR
    ANR
  • FRM
    FRM
  • Marie curie actions
    Marie curie actions
  • ERC
    ERC


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