[Neuroscience] Re: Forcing neural progenitor cells to cycle is
insufficient to alter
(by hackedyetagain from japan.com)
Fri Mar 7 11:05:44 EST 2008
Ooops, I must be losing it yet again -- this can't be of much interest to
soc.culture.zimbabwe and soc.culture.japan who I stupidly crossposted to.
In article <f269ac3e-cea6-46e2-9b88-d90172cd1081 from n58g2000hsf.googlegroups.com>,
hackedyetagain from japan.com says...
>this study suggests that controling cell proliferation is insufficient
>to prevent differentiation and exit in time. nutrient supply can't be
>a factor but perhaps certain growth factors remain elusive?
>During the development of the nervous system, neural progenitor cells
>can either stay in the pool of proliferating undifferentiated cells or
>exit the cell cycle and differentiate. Two main factors will determine
>the fate of a neural progenitor cell: its position within the
>neuroepithelium and the time at which the cell initiates
>differentiation. In this paper we investigated the importance of the
>timing of cell cycle exit on cell-fate decision by forcing neural
>progenitors to cycle and studying the consequences on specification
>and differentiation programs.
>As a model, we chose the spinal progenitors of motor neurons (pMNs),
>which switch cell-fate from motor neurons to oligodendrocytes with
>time. To keep pMNs in the cell cycle, we forced the expression of G1-
>phase regulators, the D-type cyclins. We observed that keeping neural
>progenitor cells cycling is not sufficient to retain them in the
>progenitor domain (ventricular zone); transgenic cells instead migrate
>to the differentiating field (mantle zone) regardless of cell cycle
>exit. Cycling cells located in the mantle zone do not retain markers
>of neural progenitor cells such as Sox2 or Olig2 but upregulate
>transcription factors involved in motor neuron specification,
>including MNR2 and Islet1/2. These cycling cells also progress through
>neuronal differentiation to axonal extension. We also observed mitotic
>cells displaying all the features of differentiating motor neurons,
>including axonal projection via the ventral root. However, the rapid
>decrease observed in the proliferation rate of the transgenic motor
>neuron population suggests that they undergo only a limited number of
>divisions. Finally, quantification of the incidence of the phenotype
>in young and more mature neuroepithelium has allowed us to propose
>that once the transcriptional program assigning neural progenitor
>cells to a subtype of neurons is set up, transgenic cells progress in
>their program of differentiation regardless of cell cycle exit.
>Our findings indicate that maintaining neural progenitor cells in
>proliferation is insufficient to prevent differentiation or alter cell-
>fate choice. Furthermore, our results indicate that the programs of
>neuronal specification and differentiation are controlled
>independently of cell cycle exit.
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