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Cerebral Cortical Development and Evolution

Proliferating neurons in the dorsal pallium Dr Fernando Garcia Moreno
Proliferating neurons in the dorsal pallium

Our laboratory is situated in the Le Gros Clark Building, Department of Physiology, Anatomy and Genetics at University of Oxford.  We are interested in the interactions between the environment and the unfolding genetic program of brain development, with special attention to the cerebral cortex.

Our objectives

  1. Understand the development of early cortical circuits (with special attention to thalamocortical projections and subplate neurons).
  2. Study how progenitor/stem cells produce cerebral cortical neurons during normal embryonic development and in the adult after injury.
  3. To elucidate the normal migration and differentiation program of cortical neurons and understand their disorders.
  4. To gain insight into the evolution of these developmental mechanisms.

A functional nervous system relies on precise spatial and temporal orchestration of gene expression, billions of proper electrical and chemical connections between millions of cells, and an exact balance of cell types that navigate and integrate over great distances.  As connections form between nerve cells and their electrical properties emerge, the brain begins to process information and mediate behaviours even during embryonic life.  Some circuitry is built into the nervous system during embryogenesis; however, interactions with the world continuously update and adapt the brain's functional architecture throughout life.  The mechanisms by which these plastic changes occur appear to be a continuation of the process that sculpts the brain during development.  To understand the brain and its devastating diseases, we need to reveal the mechanisms that produce it and the ways in which it can constantly change.

Building the brain is like a house of cards. The early connections provide the foundation of the adult structure, and disruption of these may be the source of many developmental flaws. Cerebral cortical developmental disorders (including schizophrenia, autism and dyslexia) and perinatal injuries involve cortical neurons with early connectivity, and the major hindrance of progress in understanding the early neural circuits during cortical development and disease was a lack of basic knowledge on neurogenesis, cell migration and reliable markers for specific cell populations. Due to the advance of powerful approaches in gene expression analysis and the utility of models with reporter gene expressions in specific cortical cell types our knowledge of the early cortical circuits is rapidly increasing. This field benefited from recent developments in mouse genetics in generating models with subtype specific gene expression patterns, powerful cell dissection and separation methods combined with microarray and sequencing analysis.  We wish to understand neuronal integration into the early intracortical and extracortical circuitry during normal and altered cortical development.

Our team

Selected publications

Related research themes