Spatial sexual dimorphism of X and Y homolog gene expression in the human central nervous system during early male development

Biology of Sex Differences

Martin M. Johansson³  Elin Lundin¹  Xiaoyan Qian¹  Mohammadreza Mirzazadeh³  Jonatan Halvardson⁴  Elisabeth Darj²  Lars Feuk⁴  Mats Nilsson¹  Elena Jazin³ 

[1] Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden

[2] Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway

[3] Department of Organismal Biology, EBC, Uppsala University, Uppsala, Sweden

[4] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

关键词: NeuN;    SOX10;    OLIG2;    ISLET1;    NLGN4Y;    NLGN4X;    PCDH11Y;    PCDH11X;    Rolling circle amplification;    Medulla oblongata;    Cortex;    Spinal cord;    Brain;    Y chromosome;    X chromosome;    Neuroligin;    Protocadherin;    Gene expression;    Male;    Female;    Human embryo development;    Sex differences;   

Others  :  1235391
DOI  :  10.1186/s13293-015-0056-4

 received in 2015-08-19, accepted in 2015-12-29,  发布年份 2016

【 摘 要 】

Background

Renewed attention has been directed to the functions of the Y chromosome in the central nervous system during early human male development, due to the recent proposed involvement in neurodevelopmental diseases. PCDH11Y and NLGN4Y are of special interest because they belong to gene families involved in cell fate determination and formation of dendrites and axon.

Methods

We used RNA sequencing, immunocytochemistry and a padlock probing and rolling circle amplification strategy, to distinguish the expression of X and Y homologs in situ in the human brain for the first time. To minimize influence of androgens on the sex differences in the brain, we focused our investigation to human embryos at 8–11 weeks post-gestation.

Results

We found that the X- and Y-encoded genes are expressed in specific and heterogeneous cellular sub-populations of both glial and neuronal origins. More importantly, we found differential distribution patterns of X and Y homologs in the male developing central nervous system.

Conclusions

This study has visualized the spatial distribution of PCDH11X/Y and NLGN4X/Y in human developing nervous tissue. The observed spatial distribution patterns suggest the existence of an additional layer of complexity in the development of the male CNS.

【 授权许可】

   
2016 Johansson et al.

【 图 表 】

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