The modulatory effects of bHLH transcription factors with the Wnt/beta-catenin pathway on differentiation of neural progenitor cells derived from neonatal mouse anterior subventricular zone.
The subventricular zone (SVZ) located adjacent to the lateral ventricles is the major site where neural progenitor cells (NPCs) are concentrated in the adult brain. NPCs in the anterior subventricular zone (SVZa) generate neuronal precursors and migrate along a highly localized pathway--the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate into interneurons. To investigate the modulatory effects of basic helix-loop-helix (bHLH) transcription factors on differentiation from SVZa NPCs, we firstly examined the distribution of bHLH family members (Mash1, Id2, and Hes1) in cultured mouse SVZa NPCs and evaluated their regulatory effects on differentiation by transfection with Mash1, Id2, or Hes1 eukaryotic expression plasmid. Furthermore, we assessed the effects of bHLH transcription factors on the expression of downstream molecules of the Wnt/beta-catenin pathway, beta-catenin and (Glycogen synthase kinase-3beta). Our results demonstrated that Mash1, Id2, Hes1 were all widely expressed in in vitro progenies from mouse SVZa NPCs. Analyses of SVZa NPCs transfected with eukaryotic expression plasmids showed that Mash1 promoted neuronal differentiation from SVZa NPCs, while Id2 and Hes1 repressed neuronal differentiation. In addition, we found that Id2 and Hes1 simulated expression of beta-catenin and GSK-3beta, while Mash1 inhibited their expression. Our results suggest that the classic bHLH transcription factors, Mash1, Id2 and Hes1, play important roles in the regulation of differentiation from SVZa NPCs. This modulation is possibly mediated by a coordination of bHLH and Wnt/beta-catenin signaling.
Zhang
ChunQing
C
Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, 2-V Xinqiao Street, Chongqing 400037, China.
Zhang
ZhiYuan
Z
Shu
HaiFeng
H
Liu
ShiYong
S
Song
YeChun
Y
Qiu
KeJun
K
Yang
Hui
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D018398:Homeodomain Proteins / Q000378:metabolism; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D000072056:Transcription Factor HES-1; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D018398:Homeodomain Proteins; D051797:Inhibitor of Differentiation Protein 2; D000072056:Transcription Factor HES-1; D051153:Wnt Proteins; D051176:beta Catenin; C499317:Ascl1 protein, mouse; C489734:Hes1 protein, mouse; C497452:Idb2 protein, mouse; C000605507:Gsk3b protein, mouse