The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors

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 XiangYing Mei Peng, Xiang yu Cao, Yi Li, Xiao dong Shi, Lin Gan, Bing Su

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere50375
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 30 2012
Externally publishedYes

Fingerprint

interleukin-3
Interleukin-3
Brain
Genes
brain
genes
Sex Characteristics
Neurons
Interleukin-3 Receptors
neurons
promoter regions
receptors
Estrogen Receptors
Population
Polymorphism
gender differences
sexual dimorphism
estrogens
Estrogens
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors. / Luo, Xiong jian; Li, Ming; Huang, Liang; Nho, Kwangsik; Deng, Min; Chen, Qiang; Weinberger, Daniel R.; Vasquez, Alejandro Arias; Rijpkema, Mark; Mattay, Venkata S.; Saykin, Andrew J.; Shen, Li; Fernández, Guillén; Franke, Barbara; Chen, Jing chun; Chen, Xiang ning; Wang, Jin kai; Xiao, Xiao; Qi, Xue bin; Xiang, Kun; Peng, Ying Mei; Cao, Xiang yu; Li, Yi; Shi, Xiao dong; Gan, Lin; Su, Bing.

In: PloS one, Vol. 7, No. 11, e50375, 30.11.2012.

Research output: Contribution to journalArticle

Luo, XJ, Li, M, Huang, L, Nho, K, Deng, M, Chen, Q, Weinberger, DR, Vasquez, AA, Rijpkema, M, Mattay, VS, Saykin, AJ, Shen, L, Fernández, G, Franke, B, Chen, JC, Chen, XN, Wang, JK, Xiao, X, Qi, XB, Xiang, K, Peng, YM, Cao, XY, Li, Y, Shi, XD, Gan, L & Su, B 2012, 'The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors', PloS one, vol. 7, no. 11, e50375. https://doi.org/10.1371/journal.pone.0050375
Luo, Xiong jian ; Li, Ming ; Huang, Liang ; Nho, Kwangsik ; Deng, Min ; Chen, Qiang ; Weinberger, Daniel R. ; Vasquez, Alejandro Arias ; Rijpkema, Mark ; Mattay, Venkata S. ; Saykin, Andrew J. ; Shen, Li ; Fernández, Guillén ; Franke, Barbara ; Chen, Jing chun ; Chen, Xiang ning ; Wang, Jin kai ; Xiao, Xiao ; Qi, Xue bin ; Xiang, Kun ; Peng, Ying Mei ; Cao, Xiang yu ; Li, Yi ; Shi, Xiao dong ; Gan, Lin ; Su, Bing. / The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors. In: PloS one. 2012 ; Vol. 7, No. 11.
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AU - Nho, Kwangsik

AU - Deng, Min

AU - Chen, Qiang

AU - Weinberger, Daniel R.

AU - Vasquez, Alejandro Arias

AU - Rijpkema, Mark

AU - Mattay, Venkata S.

AU - Saykin, Andrew J.

AU - Shen, Li

AU - Fernández, Guillén

AU - Franke, Barbara

AU - Chen, Jing chun

AU - Chen, Xiang ning

AU - Wang, Jin kai

AU - Xiao, Xiao

AU - Qi, Xue bin

AU - Xiang, Kun

AU - Peng, Ying Mei

AU - Cao, Xiang yu

AU - Li, Yi

AU - Shi, Xiao dong

AU - Gan, Lin

AU - Su, Bing

PY - 2012/11/30

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