Transcription Factor Expression and Notch-Dependent Regulation of Neural Progenitors in the Adult Rat Spinal Cord
| Autor: | Toshio Kitamura, Michiya Sugimori, Hidetaka Kosako, Motoshi Nagao, Gerry Weinmaster, Hirofumi Nakatomi, Masato Nakafuku, Kozo Nakamura, Naoya Yamamoto, Shin Ichi Yamamoto, Yo-ichi Nabeshima, Hirohide Takebayashi |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Notch signaling pathway Biology Rats Sprague-Dawley OLIG2 Animals Regeneration ARTICLE Cells Cultured Homeodomain Proteins Neurons Receptors Notch Stem Cells General Neuroscience Helix-Loop-Helix Motifs Neurogenesis Membrane Proteins Axotomy Cell Differentiation Antigens Differentiation Immunohistochemistry Embryonic stem cell Neural stem cell Rats Homeobox Protein Nkx-2.2 Gene Expression Regulation Spinal Cord NEUROD1 PAX6 Stem cell Neuroglia Neuroscience Signal Transduction Transcription Factors |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Recent studies have demonstrated that neural stem cells and other progenitors are present in the adult CNS. Details of their properties, however, remain poorly understood. Here we examined the properties and control mechanisms of neural progenitors in the adult rat spinal cord at the molecular level. Adult and embryonic progenitors commonly expressed various homeodomain-type (Pax6, Pax7, Nkx2.2, and Prox1) and basic helix–loop–helix (bHLH)-type (Ngn2, Mash1, NeuroD1, and Olig2) transcriptional regulatory factorsin vitro. Unlike their embryonic counterparts, however, adult progenitors could not generate specific neurons that expressed markers appropriate for spinal motoneurons or interneurons, including Islet1, Lim1, Lim3, and HB9. Cells expressing the homeodomain factors Pax6, Pax7, and Nkx2.2 also emergedin vivoin response to injury and were distributed in unique patterns in the lesioned spinal cord. However, neither the expression of the neurogenic bHLH factors including Ngn2, Mash1, and NeuroD1 nor subsequent generation of new neurons could be detected in injured tissue. Our results suggest that signaling through the cell-surface receptor Notch is involved in this restriction. The expression of Notch1in vivowas enhanced in response to injury. Furthermore, activation of Notch signalingin vitroinhibited differentiation of adult progenitors, whereas attenuation of Notch signals and forced expression of Ngn2 significantly enhanced neurogenesis. These results suggest that both the intrinsic properties of adult progenitors and local environmental signals, including Notch signaling, account for the limited regenerative potential of the adult spinal cord. |
| Databáze: | OpenAIRE |
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