Thursday, August 17, 2006

The brain-testes connection   posted by Coffee Mug @ 8/17/2006 09:17:00 PM

There has been some interest of late in the similarity between gene expression profiles in brain and testis. Why on earth would you make the same genes in these wildly different tissues? First off, there is this paper which confirms that there is, in fact, a significant overlap between human brain and testis expression profiles. A lot of the overlapping genes are named things like Ribosomal Protein L30. So a large portion of the overlap is genes involved in protein synthesis. I have no idea why. I'm not really down with their discussion though. They make a few suggestions that the expression overlap has something to do with human speciation, but they did no comparative genomics. I'm willing to bet that the similarity between brain and testis gene expression goes back at least to the origin of mammals if not further.

Some things to consider when analyzing overall expression profiles in brain and testes:
  • The brain is mostly glia, and some classes of glia share a lot of properties with immune cells.
  • The brain is diverse and contains many cell-types, so mashing up a whole brain to look for gene levels is bound to give you a teensy signal-to-noise ratio.
  • Tissues that are immune-privileged include: Central Nervous System, Eye, Testes, Uterus
This last one may be really important for understanding the overlap. Immune privilege means that there is a barrier built up between the tissue and the blood, such that the immune system (T cells, etc..) doesn't usually invade. One could imagine that building this barrier requires some certain common cellular regulation. Also, the exclusion of T cells would make these areas seem unique.

While looking around for brain-testes lit, I found Jenny Graves. She studies the evolution of sex determination. She says that SRY, the testes-determining factor, is actually a degraded version of SOX3, a transcription factor that is expressed in the developing chicken, mouse, and human nervous systems. The two known human cases of SOX3 disruption are boys with mental retardation. SOX3 is supposed to be a negative regulator of SOX9 function, and SRY may get in the way of what SOX3 is trying to do by binding DNA that SOX3 might like to bind to. Recall that SOX9 is very important for differentiation of Sertoli cells, the cells that surround developing spermies and keep them safe and warm. Interestingly, Sertoli cells also form the Blood-Testes-Barrier, so they are the source of immune privilege. I recommend reading a Jenny Graves review. I just read this one.

Update: Brain-testes overlap paper in gnxp-forum.