| First Author | Bohrer C | Year | 2015 |
| Journal | EMBO J | Volume | 34 |
| Issue | 22 | Pages | 2804-19 |
| PubMed ID | 26438726 | Mgi Jnum | J:227774 |
| Mgi Id | MGI:5702794 | Doi | 10.15252/embj.201591118 |
| Citation | Bohrer C, et al. (2015) The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes. EMBO J 34(22):2804-19 |
| abstractText | Adult neural stem/precursor cells (NSPCs) of the subventricular zone (SVZ) are an endogenous source for neuronal replacement in CNS disease. However, adult neurogenesis is compromised after brain injury in favor of a glial cell fate, which is mainly attributed to changes in the NSPC environment. Yet, it is unknown how this unfavorable extracellular environment translates into a transcriptional program altering NSPC differentiation. Here, we show that genetic depletion of the transcriptional regulator Id3 decreased the number of astrocytes generated from SVZ-derived adult NSPCs in the cortical lesion area after traumatic brain injury. Cortical brain injury resulted in rapid BMP-2 and Id3 up-regulation in the SVZ stem cell niche. Id3(-/-) adult NSPCs failed to differentiate into BMP-2-induced astrocytes, while NSPCs deficient for the Id3-controlled transcription factor E47 readily differentiated into astrocytes in the absence of BMP-2. Mechanistically, E47 repressed the expression of several astrocyte-specific genes in adult NSPCs. These results identify Id3 as the BMP-2-induced transcriptional regulator, promoting adult NSPC differentiation into astrocytes upon CNS injury and reveal a molecular link between environmental changes and NSPC differentiation in the CNS after injury. |
