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Bio
My team takes a multidisciplinary approach, using a range of neuroanatomical, electrophysiological, cell biological, molecular biological, transplantation, genetic and transgenic methods to analyse mechanisms regulatingevents that occur during the pre- and post-natal development of cortex in various species.
We have demonstrated that the newborn cerebral cortex initially overproduces axonal connections, many of which link cortical sites that are not linked in the adult.
The mature pattern of connections emerges from this exuberant population by withdrawal of axons and death of inappropriately connected cells. We proposed that specific cortical connections develop on the basis of trial-and-error.
Axons may grow in a random fashion and may try to connect to many sites, but only those that happen to reach an appropriate target succeed in maintaining their connection.
We extended these observations through the application of quantitative methods and computer modelling, culminating in the publication of a more detailed and modified version of the original “trial-and-error” theory.
This encompassed the later observation that aspects of the development of association connections not studied in my earlier work are guided from the outset.
We have used cell and tissue culture methods to show that cortex releases growth factors that can influence and may guide the growth and survival of neurons during preand post-natal development.
Mutant mice were used to demonstrate that these growth factors include at least one member of the neurotrophin family. We have demonstrated crucial requirements for transcription factors in controlling forebrain development.
Our results demonstrate that the transcription factor, Pax6, controls cell proliferation, migration and differentiation in the embryonic neocortex, and that it regulates the growth of axons from the embryonic thalamus to the cerebral cortex.
Using genetics, transgenics, chimaeras and transplantation methods we have provided convincing evidence that the mechanisms by which Pax6 regulates these processes involves the control of molecules on the surface of forebrain cells.
Our current hypothesis is that Pax6 controls the expression of receptors that allow cells to respond correctly to signals from other cells during development.
Research Interests
Papers共 63 篇Author StatisticsCo-AuthorSimilar Experts
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bioRxiv (Cold Spring Harbor Laboratory) (2022)
Shane O'Sullivan,Marion Bonneau,Philippe Gautier,Yasmin Singh,Helen Torrance, Daniel L. McCarthney, Hansjuergen Volkmer,Maarten Loos, Kathyrn L. Evans,Colin A. Semple,Siddharthan Chandran,Michel Didier,
semanticscholar(2018)
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Rowena Smith,Yu-Ting Huang,Tian Tian, Dominika Vojtasova, Oscar Mesalles-Naranjo,Steven M Pollard,Thomas Pratt,David J Price,Vassiliki Fotaki
Elaine Fletcher,Jean Wade,Petrina A Georgala,Trudi L Gillespie,David J Price, Elizabeth Pilley, Julie-Clare Becher
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