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The radial edifice of cortical architecture: from neuronal silhouettes to genetic engineering.

ABSTRACT: The developmental principles that establish the columnar edifice of the cerebral cortex underlie its evolution and dictate its physiological operations and cognitive capacity. This article contrasts the initial discoveries made by Ramón y Cajal and his contemporaries, based on the ingenious interpretation of neuronal shapes and their relationships using the Golgi method, with new insights based on the application of the most advanced methods of molecular biology and genetics. We can now propose a realistic model of how the sequence of gene expression, cascade of multiple molecular pathways and cell-cell interactions establish the number of neurons, guide their migration and allocation into proper regions and determine their differentiation into specific phenotypes that establish specific synaptic connections. The findings obtained from different levels of analyses sustain the radial unit hypothesis as a useful framework for understanding the mechanisms of cortical development and its evolution as an organ of thought.

SUBMITTER: Rakic P

PROVIDER: S-EPMC2203611 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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The radial edifice of cortical architecture: from neuronal silhouettes to genetic engineering.

Rakic Pasko P

Brain research reviews 20070331 2

The developmental principles that establish the columnar edifice of the cerebral cortex underlie its evolution and dictate its physiological operations and cognitive capacity. This article contrasts the initial discoveries made by Ramón y Cajal and his contemporaries, based on the ingenious interpretation of neuronal shapes and their relationships using the Golgi method, with new insights based on the application of the most advanced methods of molecular biology and genetics. We can now propose ...[more]

PMID: 17467805

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Project description:BACKGROUND:The genetic architecture of a quantitative trait influences the phenotypic response to natural or artificial selection. One of the main objectives of genetic mapping studies is to identify the genetic factors underlying complex traits and understand how they contribute to phenotypic expression. Presently, we are good at identifying and locating individual loci with large effects, but there is a void in describing more complex genetic architectures. Although large networks of connected genes have been reported, there is an almost complete lack of information on how polymorphisms in these networks contribute to phenotypic variation and change. To date, most of our understanding comes from theoretical, model-based studies, and it remains difficult to assess how realistic their conclusions are as they lack empirical support. RESULTS:A previous study provided evidence that nearly half of the difference in eight-week body weight between two divergently selected lines of chickens was a result of four loci organized in a 'radial' network (one central locus interacting with three 'radial' loci that, in turn, only interacted with the central locus). Here, we study the relationship between phenotypic change and genetic polymorphism in this empirically detected network. We use a model-free approach to study, through individual-based simulations, the dynamic properties of this polymorphic and epistatic genetic architecture. The study provides new insights to how epistasis can modify the selection response, buffer and reveal effects of major loci leading to a progressive release of genetic variation. We also illustrate the difficulty of predicting genetic architecture from observed selection response, and discuss mechanisms that might lead to misleading conclusions on underlying genetic architectures from quantitative trait locus (QTL) experiments in selected populations. CONCLUSION:Considering both molecular (QTL) and phenotypic (selection response) data, as suggested in this work, provides additional insights into the genetic mechanisms involved in the response to selection. Such dissection of genetic architectures and in-depth studies of their ability to contribute to short- or long-term selection response represents an important step towards a better understanding of the genetic bases of complex traits and, consequently, of the evolutionary properties of populations.

Dataset Information

The radial edifice of cortical architecture: from neuronal silhouettes to genetic engineering.

Publications

The radial edifice of cortical architecture: from neuronal silhouettes to genetic engineering.

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