Expression of Disabled 1 suppresses astroglial differentiation in neural stem cells.
Disabled 1 (Dab1), a cytoplasmic adaptor protein expressed predominantly in the CNS, transduces a Reelin-initiated signaling that controls neuronal migration and positioning during brain development. To determine the role of Dab1 in neural stem cell (NSC) differentiation, we established a culture of neurospheres derived from the embryonic forebrain of the Dab1(-/-) mice, yotari. Differentiating Dab1(-/-) neurospheres exhibited a higher expression of GFAP, an astrocytic marker, at the expense of neuronal markers. Under Dab1-deficient condition, the expression of NeuroD, a transcription factor for neuronal differentiation, was decreased and the JAK-STAT pathway was evidently increased during differentiation of NSC, suggesting the possible involvement of Dab1 in astrocyte differentiation via JAK-STAT pathway. Notably, expression of neural and glial markers and the level of JAK-STAT signaling molecules were not changed in differentiating NSC by Reelin treatment, indicating that differentiation of NSC is Reelin-independent. Immunohistochemical analyses showed a decrease in the number of neurons and an increase in the number of GFAP-positive cells in developing yotari brains. Our results suggest that Dab1 participates in the differentiation of NSCs into a specific cell lineage, thereby maintaining a balance between neurogenesis and gliogenesis.
Department of Anatomy, School of Medicine, Ajou University, Suwon, 443-749, South Korea.
Il-Sun
IS
Kwon
Sung-Kuk
SK
Cho
Min-Ji
MJ
Kim
Ming-Jer
MJ
Tsai
Noriaki
N
Mitsuda
Haeyoung
H
Suh-Kim
Young-Don
YD
Lee
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D007381:Intermediate Filament Proteins; D053612:Janus Kinases; D009419:Nerve Tissue Proteins; D064231:Nestin; D034741:RNA, Small Interfering; D000091042:Reelin Protein; D050791:STAT Transcription Factors; D012697:Serine Endopeptidases; C103773:Dab1 protein, mouse; C577485:Nes protein, mouse; C093564:Neurogenic differentiation factor 1; C000717128:Reln protein, mouse