Big Nuts

I thought that the people who read my blog (all two of you) might like to see an example of what it is that I study. My lab focuses on sex determination and gonad organogenesis - or rather, how the decision is made to become male or female, how the organism's cells remember this decision, and how the process plays out. Since humans become male or female depending on whether their gonad develops as a testis or an ovary, we study the particular cellular decisions that must be made for the gonad to commit to a testicular or ovarian fate.

Sometimes the signals get mixed and the decision isn't clear, and as a result you end up with a hermaphrodite, or intersex organism - having both male and female parts. Other times the right signal is masked or lost entirely such that the opposite decision is made and sex reversal occurs.

Inside the gonad (both testis and ovary) special cells, called germ cells, give rise to either sperm or oocytes which are responsible for generating the next generation. These cells represent the immortal line, and through them we can all be traced back to the very beginnings of cellular life on this planet. My focus is on these germ cells, and how they decide to behave accordingly depending on which kind of gonad they end up in.

Particularly I study a mouse that has a mutation that causes germ cells to do something considered very bad in humans - turn into cancer! Germ cells are so special, and powerful, that they are set aside at very early stages during development - so early that there is no gonad for them to live in yet. So they wait for the embryo to develop further and begin to migrate to the inside, up through the hidgut and finally to the site of the emerging gonadal tissue just in the nick of time.

In my mutant males, the germ cells are pretty sick before they get to the gonad and only a few make it. Those that make it to a testis end up transforming a few days later and turning into early cancer cells. By birth the mutant testis is already sick with these growing cells, forming an early tumor. Two weeks after birth the testes look monstrous - even the name for this kind of tumor, teratoma, actually comes from the Greek meaning 'monster'. Here's a picture of normal mouse testes and then a pair of testes from my mutants:



Overall my goal is to study germ cells and learn about how this gene affects their development. One of my sub-goals is to figure out how and why this particular mutation causes these kinds of tumors at this particular point during development.

Cool, huh?

The XX --- XY divide ... evidence from Turner's patients.

I thought it would be fun to enter a science post ... and not just any science post, but something really cool and taken from about a decade ago. I work in a lab that focuses on mammalian sex determination, and there are many interesting debates that are tackled on a day-to-day basis. My boss brought this study to my attention earlier this month, and it was concerning research published in 1997.

David Skuse is very creative and wanted to find a way to see if there are differences in sex chromosomes depending on if we inherit them from mom or dad. In humans, two X chromosomes (XX) leads to female development, and an X and Y chromosome (XY) lead to male development. As such, when your parents used their gametes to make you, your mom HAD to pass on an X chromosome to you. If you are female, then dad happened to give you his X; alternatively, if you are male, then dad happened to give you his Y.

Well sometimes things don't go as planned, and instead of passing one of these on to you, a parent's gamete fails to deliver with any sex chromsome at all. Now, if you only receive a Y chromsome, you can't develop at all - the embryo can't survive. But if you only receive one X chromosome, you'll grow up just fine, though with a few minor problems. This scenario (45,X) is referred to as Turner's syndrome. These individuals, while only having one X chromsome, will develop physically as females. But interestingly, the single X chromosome could come from mom OR dad.

David Skuse saw this special group of individuals as a fantastic opportunity to explore some questions we have about human (and sexually dimorphic) behavior. In general, we think of girls as having better social cognitive function than boys. But could there be a genetic basis for this? The Y chromosome is very tiny in comparison to the X, so there are actually many genes that only exist on the X (which is important because you ALWAYS get two copies of every gene, one from mom and one from dad, unless you are a boy and only have one X). To keep things fairly at an equilibrium, girls actually INACTIVATE one of their X chromosomes so that they only use one, just like the boys - though this inactivation process is random. In the end, ALL boys use the X that their mom gave them, but girls use either the X from the mom or from the dad. This is where it gets interesting.

David Skuse hypothesized that maybe these X chromosomes are not the same - maybe they are partly responsible for different behaviors that we associate with the different sexes. He looked at Turner's syndrome patients and saw that some got their X from mom, while others got theirs from dad. He did a basic and thorough study to determine the social cognitive skills, comparing patients who got their X from mom directly to those who got their X from dad. His results are very interesting!


Subjects who received their X chromsome from the mom, scored much higher for social-cognitive DISFUNCTION! Individuals receiving their X chromsome from dad were much better adjusted and had better social-cognitive ratings. When compared to normal individuals, normaly XX girls have better social-cognitive skills than normal XY boys. This supports the notion that something on the X chromosome influences this behavior - XY boys have to get their X from the mom, and they do perform poorly, like the Turner's patients receiving the X from the mom. Alternatively, XX girls can use the X from either mom or dad, and they do much better with social-cognictive skills, like the Turner's patients receiveing the X from the dad.

This simple, yet elegant, study revealed the presence of an X-linked imprinted locus that affects social-cognitive skills in human sexually dimorphic behavior and supported the hypothesis of a genetic basis for this complex phenotype. Additionally, to quote the last sentence of the abstract, "If expressed only from the X chromosome of paternal origin, the existence of this locus could explain why 46,XY males (whose single X chromosome is maternal) are more vulnerable to developmental disorders of language and social cognition, such as autism, than are 46,XX females."

So remember, ladies - you have your fathers to thank (in part) for your superior social-cognitive skills. And guys, you can at least have the satisfaction of knowing that you'll be helping your daughter out, should you indeed 'decide' to pass on your X chromosome.