Specific glial populations regulate hippocampal morphogenesis.
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.
Barry
Guy
G
The University of Queensland, Queensland Brain Institute, and School of Biomedical Sciences, Brisbane, 4067, Australia.
Piper
Michael
M
Lindwall
Charlotta
C
Moldrich
Randal
R
Mason
Sharon
S
Little
Erica
E
Sarkar
Anindita
A
Tole
Shubha
S
Gronostajski
Richard M
RM
Richards
Linda J
LJ
D000367:Age Factors; D000818:Animals; D002452:Cell Count; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology*; D006657:Histones / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D051839:NFI Transcription Factors / Q000172:deficiency; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D013997:Time Factors
D027341:Excitatory Amino Acid Transporter 1; D005904:Glial Fibrillary Acidic Protein; D006657:Histones; D007381:Intermediate Filament Proteins; D051839:NFI Transcription Factors; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C493393:Slc1a3 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse; D018698:Glutamic Acid