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Biol Sex Differ. 2016 Jan 12;7:5. doi: 10.1186/s13293-015-0056-4. eCollection 2016.

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 Johansson, Elin Lundin, Xiaoyan Qian, Mohammadreza Mirzazadeh, Jonatan Halvardson, Elisabeth Darj, Lars Feuk, Mats Nilsson, Elena Jazin

Affiliations

  1. Department of Organismal Biology, EBC, Uppsala University, Uppsala, Sweden.
  2. Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
  3. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  4. Department of Women's and Children's Health, International Maternal and Child Health, Uppsala University, Uppsala, Sweden.
  5. Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.

PMID: 26759715 PMCID: PMC4710049 DOI: 10.1186/s13293-015-0056-4

Abstract

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.

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

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