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Role of axon guidance molecules

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Team leader: Alain Chedotal

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Introduction

We explore the role of axon guidance molecules in the regulation of cell-cell interactions during normal development and in pathologies. We also study the function and evolution of commissural connections in the vertebrate central nervous system.

Presentation

Nervous systems are composed of a network of synaptic connections among excitable cells. This network develops as axons extend from presynaptic neurons and grow often long distances to reach their correct postsynaptic partners. Neuronal migration and myelination are also key processes for the formation and stabilization of neuronal connections. For years, neurobiologists have tried to uncover the mechanisms controlling axon guidance. It was found that these are highly conserved between neurons and during evolution. It was also shown that axonal connections are plastic and can be modified during normal physiological processes and in pathological conditions.

From its beginning, our group has studied the development of neuronal connections in the central nervous system (CNS). The field has also gained even more interest in the scientific community when mounting evidence showed that in the nervous system, axon guidance molecules control also other processes (e.g. migration, myelination, apoptosis, plasticity) and that outside the brain they regulate cell communication and cell-cell interaction in many organs during normal development and in pathological conditions such as cancer. Our past and current work aimed at obtaining an extensive view of the role of axon guidance molecules in the vertebrate nervous system. We have mostly studied the function of the Slits and their Roundabout (Robo) receptors and of class 6 transmembrane semaphorins and their Plexin-A receptors.

The aim of our research project is to study extensively the function of axon guidance molecules in the developing and adult central nervous system (CNS). We primarily focus on semaphorins, slits and their receptors and on a few model systems (visual system, cerebellar system, commissural neurons). We  try to understand the cellular and molecular mechanisms controlling the development of retinal layers, neural crest cells and brain commissures. We also try to understand how the expression of Robo receptors is regulated. We have generated several conditional knockout lines that are allowing us to start addressing the function of Slit/Robo signaling in postnatal neurogenesis, neo-angiogenesis and cancer. We also study the regulation of cell-cell interactions during myelination and remyelination using novel genetic methods. Last, we try to develop new tools to promote axonal regeneration in the optic nerve and cornea.


Research areas

  • Development of retinal connectivity and optic nerve regeneration.

  • Development, function and evolution of brain commissures.

  • Molecular control of granule cell migration by semaphorins and plexins.

  • Mechanisms controlling the differentiation and specification of neural crest cells.

  • Role of axon guidance molecules in angiogenesis and ocular vasoproliferative diseases.

  • Innervation of the cornea and cornea transplantation.

  • Regulation of cell-cell interactions during myelination and remyelination by novel genetic methods.



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  • ANR
    ANR
  • FRM
    FRM
  • FRC
    FRC
  • Sorbonne université
    Sorbonne université
  • Ela
    Ela


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