In:
eLife, eLife Sciences Publications, Ltd, Vol. 3 ( 2014-06-14)
Abstract:
After an egg has been fertilized, it undergoes a series of divisions to produce a ball of cells known as a blastocyst. The cells within the blastocyst are pluripotent stem cells, which have the potential to become many different types of cell. After a few days, the stem cells organize into three layers—an innermost layer called the endoderm, a middle layer of mesoderm, and an outer layer of ectoderm—that ultimately give rise to different types of tissues. The brain and nervous system are formed from cells in the neuroectoderm, which is part of the ectoderm. Now, Zhu et al. have shown that a transcription factor called Pou3f1 triggers stem cells within a region of the ectoderm to turn into neural progenitor cells, thereby generating the neuroectoderm. These neural progenitor cells then go on to become neurons and glial cells that make up the brain and nervous system. Using a virus to reduce levels of Pou3f1 in embryonic stem cells grown in a dish led to a drop in the number of stem cells that committed to neural progenitor cells. Overexpressing Pou3f1 in the stem cells restored the number of neural progenitor cells. Together these results showed that Pou3f1 is both necessary and sufficient for the conversion of embryonic stem cells into future neurons and glia. The same result was seen when embryonic stem cells containing either reduced or elevated levels of Pou3f1 were injected into 2.5-day-old mouse blastocysts, which were then implanted into surrogate females. The resulting embryos comprised some cells with normal levels of Pou3f1, and others with either too little or too much. Cells with elevated Pou3f1 mostly became neural progenitors, whereas those with reduced levels rarely did so. Gene expression studies revealed that Pou3f1 promoted the formation of neural progenitor cells by activating the expression of pro-neuronal genes inside the stem cells, and by blocking anti-neuronal pathways called Wnt/BMP signaling cascades initiated outside the cells. By revealing the two roles of Pou3f1, Zhu et al. have increased our understanding of one of the earliest stages of nervous system development. Further work is required to determine exactly how Pou3f1 exerts its effects and, in particular, whether it performs its two roles simultaneously or in sequence.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.02224.001
DOI:
10.7554/eLife.02224.002
DOI:
10.7554/eLife.02224.003
DOI:
10.7554/eLife.02224.004
DOI:
10.7554/eLife.02224.005
DOI:
10.7554/eLife.02224.006
DOI:
10.7554/eLife.02224.007
DOI:
10.7554/eLife.02224.008
DOI:
10.7554/eLife.02224.009
DOI:
10.7554/eLife.02224.010
DOI:
10.7554/eLife.02224.011
DOI:
10.7554/eLife.02224.012
DOI:
10.7554/eLife.02224.013
DOI:
10.7554/eLife.02224.014
DOI:
10.7554/eLife.02224.015
DOI:
10.7554/eLife.02224.016
DOI:
10.7554/eLife.02224.017
DOI:
10.7554/eLife.02224.018
DOI:
10.7554/eLife.02224.019
DOI:
10.7554/eLife.02224.020
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2014
detail.hit.zdb_id:
2687154-3
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