title: Spatial sexual dimorphism of X and Y homolog gene expression in the human central nervous system during early male development.
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.
authors.affiliation: Department of Organismal Biology, EBC, Uppsala University, Uppsala, Sweden.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Johansson
authors.affiliation: Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Lundin
authors.affiliation: Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Organismal Biology, EBC, Uppsala University, Uppsala, Sweden.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Mirzazadeh
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Halvardson
authors.affiliation: Department of Women's and Children's Health, International Maternal and Child Health, Uppsala University, Uppsala, Sweden.|Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Darj
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
authors.affiliation: Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: Department of Organismal Biology, EBC, Uppsala University, Uppsala, Sweden.
authors.forename: Elena
authors.initials: E
authors.lastname: Jazin
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