Neurogenesis in Talpha-1 tubulin transgenic mice during development and after injury.
Talpha-1 tubulin promoter-driven EYFP expression is seen in murine neurons born as early as E9.5. Double labeling with markers for stem cells (Sox 1, Sox 2, nestin), glial progenitors (S100beta, NG2, Olig2), and neuronal progenitors (doublecortin, betaIII-tubulin, PSA-NCAM) show that Talpha-1 tubulin expression is limited to early born neurons. BrdU uptake and double labeling with neuronal progenitor markers in vivo and in vitro show that EYFP-expressing cells are postmitotic and Talpha-1 tubulin EYFP precedes the expression of MAP-2 and NeuN, and follows the expression of PSA-NCAM, doublecortin (Dcx), and betaIII-tubulin. Talpha-1 tubulin promoter-driven EYFP expression is transient and disappears in most neurons by P0. Persistent EYFP expression is mainly limited to scattered cells in the subventricular zone (SVZ), rostral migratory stream, and hippocampus. However, there are some areas that continue to express Talpha-1 tubulin in the adult without apparent neurogenesis. The number of EYFP-expressing cells declines with age indicating that Talpha-1 tubulin accurately identifies early born postmitotic neurons throughout development but less clearly in the adult. Assessment of neurogenesis after stab wound injuries in the cortex, cerebellum and spinal cord of adult animals shows no neurogenesis in most areas with an increase in BrdU incorporation in glial and other non neuronal populations. An up-regulation of Talpha-1 tubulin can be seen in certain areas unaccompanied by new neurogenesis. Our results suggest that even if stem cells proliferate their ability to generate neurons is limited and caution is warranted in attributing increased BrdU incorporation to stem cells or cells fated to be neurons even in neurogenic areas.
Coksaygan
Turhan
T
Gerontology Research Center, Stem Cell Biology Unit/Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Room 4E02, Baltimore, MD 21224, USA. tcoksaygan@vetmed.umaryland.edu
Magnus
Tim
T
Cai
Jingli
J
Mughal
Mohammed
M
Lepore
Angelo
A
Xue
Haipeng
H
Fischer
Itzhac
I
Rao
Mahendra S
MS
D000818:Animals; D000941:Antigens / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D000089662:Doublecortin Protein; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D007381:Intermediate Filament Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D011509:Proteoglycans / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D002795:Choline O-Acetyltransferase; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D007381:Intermediate Filament Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1; D000076104:Oligodendrocyte Transcription Factor 2; D011509:Proteoglycans; D012794:Sialic Acids; D014404:Tubulin; D000099216:Chondroitin Sulfate Proteoglycan 4; C000714847:Dcx protein, mouse; C577485:Nes protein, mouse; C512773:Olig2 protein, mouse; C103469:polysialyl neural cell adhesion molecule; C007293:DAPI