| Title |
The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors
|
|---|---|
| Published in |
PLOS ONE, November 2012
|
| DOI | 10.1371/journal.pone.0050375 |
| Pubmed ID | |
| Authors |
Xiong-jian Luo, Ming Li, Liang Huang, Kwangsik Nho, Min Deng, Qiang Chen, Daniel R. Weinberger, Alejandro Arias Vasquez, Mark Rijpkema, Venkata S. Mattay, Andrew J. Saykin, Li Shen, Guillén Fernández, Barbara Franke, Jing-chun Chen, Xiang-ning Chen, Jin-kai Wang, Xiao Xiao, Xue-bin Qi, Kun Xiang, Ying-Mei Peng, Xiang-yu Cao, Yi Li, Xiao-dong Shi, Lin Gan, Bing Su |
| Abstract |
One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which alters the expression of IL3 by affecting the binding affinity of transcription factor SP1. Further analysis indicated that IL3 and its receptors are continuously expressed in the developing mouse brain, reaching highest levels at postnatal day 1-4. Furthermore, we found IL3 receptor alpha (IL3RA) was mainly expressed in neural progenitors and neurons, and IL3 could promote proliferation and survival of the neural progenitors. The expression level of IL3 thus played pivotal roles in the expansion and maintenance of the neural progenitor pool and the number of surviving neurons. Moreover, we found that IL3 activated both estrogen receptors, but estrogen didn't directly regulate the expression of IL3. Our results demonstrate that genetic variation in the IL3 promoter regulates human brain volume and reveals novel roles of IL3 in regulating brain development. |
Mendeley readers
The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 2% |
| Unknown | 60 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 14 | 23% |
| Researcher | 10 | 16% |
| Student > Bachelor | 9 | 15% |
| Student > Master | 5 | 8% |
| Student > Postgraduate | 4 | 7% |
| Other | 12 | 20% |
| Unknown | 7 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 12 | 20% |
| Agricultural and Biological Sciences | 12 | 20% |
| Neuroscience | 11 | 18% |
| Medicine and Dentistry | 4 | 7% |
| Immunology and Microbiology | 3 | 5% |
| Other | 6 | 10% |
| Unknown | 13 | 21% |