Phylogenetic Proximity Revealed by Neurodevelopmental Event Timings
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ORIGINAL ARTICLE
Phylogenetic Proximity Revealed by Neurodevelopmental Event Timings Radhakrishnan Nagarajan & Barbara Clancy
Published online: 23 May 2008 # Humana Press 2008
Abstract Statistical properties such as distribution and correlation signatures were investigated using a temporal database of common neurodevelopmental events in the three species most frequently used in experimental studies, rat, mouse, and macaque. There was a fine nexus between phylogenetic proximity and empirically derived dates of the occurrences of 40 common events including the neurogenesis of cortical layers and outgrowth milestones of developing axonal projections. Exponential and power-law approximations to the distribution of the events reveal strikingly similar decay patterns in rats and mice when compared to macaques. Subsequent hierarchical clustering of the common event timings also captures phylogenetic proximity, an association further supported by multivariate linear regression data. These preliminary results suggest that statistical analyses of the timing of developmental milestones may offer a novel measure of phylogenetic classifications. This may have added pragmatic value in the specific support it offers for the reliability of rat/mouse comparative modeling, as well as in the broader implications for the potential of meta-analyses using databases assembled from the extensive empirical literature.
R. Nagarajan (*) Department of Biostatistics, University of Arkansas for Medical Sciences, COPH/UAMS, Room 3234, 4301 W Markham, Slot 781, Little Rock, AR 72205-7199, USA e-mail: [email protected] B. Clancy Department of Biology, University of Central Arkansas, Conway, AR 72035, USA
Keywords Comparative neural development . Cross-species modeling . Macaque . Mouse . Neuroinformatics . Phylogeny . Rat
Introduction Although neurodevelopment occurs at dissimilar times and intervals in different mammalian species, it consists of similar events and follows remarkably conserved sequences (Finlay and Darlington 1995). For example, rats have a gestational period of 21.5 days, compared to 165 days for macaques, yet in both species ganglion cells in the retina are generated (“born”) before amacrine cells, neurons that form the cortical subplate are generated prior to neurons of the cortical laminae, and axons projecting from the retina reach the optic chiasm long before they segregate into ipsilateral and contralateral patterns in the lateral geniculate nucleus. Identification of statistical relationships in the timing of such developmental milestones (neural “events”) across various mammalian species has proved useful in understanding general concepts about evolution and development (Finlay et al. 2001; Clancy and Finlay 2003), and has been applied in a pragmatic fashion to extrapolate data obtained from well-studied experimental species to humans (Clancy et al. 2000, 2001; Clancy 2006). Recently, a database of events gleaned from the published literature, including a predictive application, was made available at http:/
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