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The Journal of Neuroscience, November 19, 2008, 28(47):12328-12340; doi:10.1523/JNEUROSCI.4000-08.2008

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Development/Plasticity/Repair
Specific Glial Populations Regulate Hippocampal Morphogenesis

Guy Barry,^1 * Michael Piper,^1 * Charlotta Lindwall,¹ Randal Moldrich,¹ Sharon Mason,¹ Erica Little,¹ Anindita Sarkar,³ Shubha Tole,³ Richard M. Gronostajski,⁴ and Linda J. Richards^1,2

¹The University of Queensland, Queensland Brain Institute, and ²School of Biomedical Sciences, Brisbane, 4067, Australia, ³Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, 400005, India, and ⁴Department of Biochemistry and The Program in Neuroscience and Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, New York 14260

Correspondence should be addressed to Linda J. Richards, The University of Queensland, Queensland Brain Institute, Brisbane QLD 4072, Australia. Email: richards{at}uq.edu.au

The hippocampus plays an integral role in spatial navigation, learning and memory, and is a major site for adult neurogenesis. Critical to these functions is the proper organization of the hippocampus during development. Radial glia are known to regulate hippocampal formation, but their precise function in this process is yet to be defined. We find that in Nuclear Factor I b (Nfib)-deficient mice, a subpopulation of glia from the ammonic neuroepithelium of the hippocampus fail to develop. This results in severe morphological defects, including a failure of the hippocampal fissure, and subsequently the dentate gyrus, to form. As in wild-type mice, immature nestin-positive glia, which encompass all types of radial glia, populate the hippocampus in Nfib-deficient mice at embryonic day 15. However, these fail to mature into GLAST- and GFAP-positive glia, and the supragranular glial bundle is absent. In contrast, the fimbrial glial bundle forms, but alone is insufficient for proper hippocampal morphogenesis. Dentate granule neurons are present in the mutant hippocampus but their migration is aberrant, likely resulting from the lack of the complete radial glial scaffold usually provided by both glial bundles. These data demonstrate a role for Nfib in hippocampal fissure and dentate gyrus formation, and that distinct glial bundles are critical for correct hippocampal morphogenesis.

Key words: hippocampal fissure; dentate gyrus; glial development; supragranular bundle; neuronal migration; gliogenesis

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Received Aug. 21, 2008; revised Sept. 25, 2008; accepted Oct. 10, 2008.

Correspondence should be addressed to Linda J. Richards, The University of Queensland, Queensland Brain Institute, Brisbane QLD 4072, Australia. Email: richards{at}uq.edu.au

This article has been cited by other articles:

				M. Piper, C. Plachez, O. Zalucki, T. Fothergill, G. Goudreau, R. Erzurumlu, C. Gu, and L. J. Richards Neuropilin 1-Sema Signaling Regulates Crossing of Cingulate Pioneering Axons during Development of the Corpus Callosum Cereb Cortex, July 1, 2009; 19(suppl_1): i11 - i21. [Abstract] [Full Text] [PDF]

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