scholarly journals Roles of the Basic Helix-Loop-Helix GenesHes1andHes5in Expansion of Neural Stem Cells of the Developing Brain

2001 ◽  
Vol 276 (32) ◽  
pp. 30467-30474 ◽  
Author(s):  
Toshiyuki Ohtsuka ◽  
Masami Sakamoto ◽  
François Guillemot ◽  
Ryoichiro Kageyama
2004 ◽  
Vol 166 (7) ◽  
pp. 963-968 ◽  
Author(s):  
Takao Setoguchi ◽  
Toru Kondo

Neural stem cell (NSC) differentiation is precisely controlled by a network of transcription factors, which themselves are regulated by extracellular signals (Bertrand et al., 2002; Shirasakiand and Pfaff, 2002). One way that the activity of such transcription factors is controlled is by the regulation of their movement between the cytosol and nucleus (Vandromme et al., 1996. Lei and Silver, 2002). Here we show that the basic helix–loop–helix transcription factor OLIG2, which has been shown to be required for motor neuron and oligodendrocyte development, is found in the cytoplasm, but not the nucleus, of astrocytes in culture and of a subset of astrocytes in the subventricular zone. We demonstrate that the accumulation of OLIG2 in the nucleus of NSCs blocks the CNTF-induced astrocyte differentiation and that the translocation of OLIG2 to the cytoplasm is promoted by activated AKT. We propose that the AKT-stimulated export of OLIG2 from the nucleus of NSCs is essential for the astrocyte differentiation.


Development ◽  
2002 ◽  
Vol 129 (1) ◽  
pp. 233-244 ◽  
Author(s):  
Seiji Hitoshi ◽  
Vincent Tropepe ◽  
Marc Ekker ◽  
Derek van der Kooy

Regional patterning in the developing mammalian brain is partially regulated by restricted gene expression patterns within the germinal zone, which is composed of stem cells and their progenitor cell progeny. Whether or not neural stem cells, which are considered at the top of the neural lineage hierarchy, are regionally specified remains unknown. Here we show that the cardinal properties of neural stem cells (self-renewal and multipotentiality) are conserved among embryonic cortex, ganglionic eminence and midbrain/hindbrain, but that these different stem cells express separate molecular markers of regional identity in vitro, even after passaging. Neural stem cell progeny derived from ganglionic eminence but not from other regions are specified to respond to local environmental cues to migrate ventrolaterally, when initially deposited on the germinal layer of ganglionic eminence in organotypic slice cultures. Cues exclusively from the ventral forebrain in a 5 day co-culture paradigm could induce both early onset and late onset marker gene expression of regional identity in neural stem cell colonies derived from both the dorsal and ventral forebrain as well as from the midbrain/hindbrain. Thus, neural stem cells and their progeny are regionally specified in the developing brain, but this regional identity can be altered by local inductive cues.


2015 ◽  
Vol 24 (11) ◽  
pp. 1297-1308 ◽  
Author(s):  
Dimitrios Cakouros ◽  
Sandra Isenmann ◽  
Sarah Elizabeth Hemming ◽  
Danijela Menicanin ◽  
Esther Camp ◽  
...  

Author(s):  
Nicoletta Kessaris ◽  
Nigel Pringle ◽  
William D Richardson

All the neurons and glial cells of the central nervous system are generated from the neuroepithelial cells in the walls of the embryonic neural tube, the ‘embryonic neural stem cells’. The stem cells seem to be equivalent to the so-called ‘radial glial cells’, which for many years had been regarded as a specialized type of glial cell. These radial cells generate different classes of neurons in a position-dependent manner. They then switch to producing glial cells (oligodendrocytes and astrocytes). It is not known what drives the neuron–glial switch, although downregulation of pro-neural basic helix–loop–helix transcription factors is one important step. This drives the stem cells from a neurogenic towards a gliogenic mode. The stem cells then choose between developing as oligodendrocytes or astrocytes, of which there might be intrinsically different subclasses. This review focuses on the different extracellular signals and intracellular responses that influence glial generation and the choice between oligodendrocyte and astrocyte fates.


2008 ◽  
Vol 22 (1) ◽  
pp. 56-64 ◽  
Author(s):  
Wenwu Li ◽  
Guoqiang Sun ◽  
Su Yang ◽  
Qiuhao Qu ◽  
Kinichi Nakashima ◽  
...  

Abstract TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.


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