TY - JOUR
T1 - Specific glial populations regulate hippocampal morphogenesis
AU - Barry, Guy
AU - Piper, Michael
AU - Lindwall, Charlotta
AU - Moldrich, Randal
AU - Mason, Sharon
AU - Little, Erica
AU - Sarkar, Anindita
AU - Tole, Shubha
AU - Gronostajski, Richard M.
AU - Richardse, Linda J.
PY - 2008/11/19
Y1 - 2008/11/19
N2 - 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.
AB - 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.
KW - Dentate gyrus
KW - Glial development
KW - Gliogenesis
KW - Hippocampal fissure
KW - Neuronal migration
KW - Supragranular bundle
UR - http://www.scopus.com/inward/record.url?scp=58149375269&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4000-08.2008
DO - 10.1523/JNEUROSCI.4000-08.2008
M3 - Article
C2 - 19020026
AN - SCOPUS:58149375269
SN - 0270-6474
VL - 28
SP - 12328
EP - 12340
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 47
ER -