MRC National Institute for Medical Research, London
Science for Health
How newborn neurons migrate
24 March 2011
Neurons in the embryonic mammalian brain are generated in progenitor zones which line the ventricles. Soon after their birth, they undergo active cell migration to reach distant locations, where they eventually form neuronal circuits. The migration of newborn neurons is a fundamental aspect of the development of the nervous system, yet its regulation is poorly understood.
Research into the molecular mechanisms controlling neuronal migration has led to the discovery of extrinsic cues, receptors and intracellular pathways that together guide neurons to their destination. Much less is known, however, of the intracellular machinery that confers a motile behaviour to newly generated neurons, and how this machinery is activated when neurons are born.
Emilie Pacary and colleagues, working in the laboratory of Francois Guillemot (pictured) in NIMR’s Divison of Molecular Neurobiology, have identified two proneural transcription factors that promote neuronal migration in the cerebral cortex. They found that the two factors act via distinct pathways, which involve different Rho GTP-binding proteins and control different phases of neuronal migration. This study has thus identified several stages during the migration of cortical neurons when transcriptional mechanisms and extracellular pathways cooperate to control the rate of migration, thus ensuring that neurons reach their destination in time to integrate into neural circuits.
Migration is a fundamental behaviour of neurons, and migration defects during brain development result in devastating conditions, including mental retardation, autism and epilepsy. Our work paves the way for the discovery of molecules that can revert pathological migration defects.
Francois Guillemot
Visualization of actin polymerization in a cortical neuron following disruption of the small GTP-binding protein Rnd3
Click image to view at full-size
Scheme of the migration of cortical neurons showing two stages (green and red) that are sensitive to regulation by different proneural factor -> small GTP-binding protein pathways.
Original article
Emilie Pacary, Julian Heng, Roberta Azzarelli, Philippe Riou, Diogo Castro, Mélanie Lebel-Potter, Carlos Parras, Donald M. Bell, Anne J. Ridley, Maddy Parsons, François Guillemot (2011)
Proneural transcription factors regulate different aspects of cortical neuron migration through Rnd-mediated inhibition of RhoA signalingNeuron 69(6): 1069-1084. Publisher abstract.
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