Left handed, or right handed?

One striking things about humans is the fact that 90% of us, when handed a pen or a tool, will use it with our right hands. And this is not a modern phenomenon. Cave paintings suggest that our ancestors tens of thousands of years ago were also inclined to use their right hands for specialist tasks. Chris Smith wanted to know how this happens...

Sebastian - My name is Sebastian Ocklenburg from Ruhr University, Bochum in Germany. The question I'm really interested in is, how does handedness develop? We know that in the population, about 90 per cent of individuals are right handed but it’s still completely unclear what determines whether somebody is left handed or right handed. The defining theory for the last couple of decades has been that handedness is determined by a single gene but we know from genetic research in the 2000s that this is very unlikely. So in the 1990s, a researcher named Peter Hepper had the theory that handedness might not be determined by the cortex but by the spinal cord because it was found that embryos already show a right handed preference for motor movements during a developmental phase in which the spinal cord is not connected to the motor cortex.

Chris - What did you do then to try to see how the spinal cord might be arriving at that situation of that right hand sided dominance in order to be future right handed?

Sebastian - One of the major theories about development of handedness is that gene expression asymmetries might play a role here. so, this is what we look at. We try to find genes that were expressed asymmetrically in the spinal cord. If there are expression asymmetries, that might be an explanation for behavioural asymmetries later in life.

Chris - How did you study that?

Sebastian - So, we looked at tissue samples from the spinal cord, from human foetuses obtained from a gynaecological clinic. Those were from week 8, 10, and 12. So we looked at genes now, they were expressed on the left and right spinal cord. We also performed epigenetic analysis. So we looked at asymmetries in gene methylations and expression of micro-RNAs.

Chris - So what you're saying is that the genetic code may well be the same in an individual who’s right and left handed but you can actually change how turned on or turned off certain genes are, and also, the epigenetic markers which are added to the genes could be different on the right and the left. That could account for the handedness even though the genetic messages are the same.

Sebastian - Exactly. So, we think this might be one of the reasons why previous researchers have found so few results when looking at genetic variation exactly that of such processes might switch on or switch off, or modify gene expression which then leads to variation in key structures in the central nervous system that modified the behavioural phenotype. You cannot see that from just looking at the genetic variation.

Chris - Was that clear? Could you see that there was a difference in the way the genes were being turned on and how much they were turned on on the right versus the left?

Sebastian - Yeah, we found that these processes are very much dependent on the time point where we look at it. So if you look at the time point where the foetuses show this right side preference for the first time to see a huge asymmetry in gene expression also in these epigenetics processes which gets less and less the further it proceeds in development.

Chris - Now famously, in his book Right Hand, Left Hand, Chris McManus who did literally write the book on left handedness since about the 1980s, he highlights in that book that asymmetry begets asymmetry. In other words, just because you were found an asymmetry in the gene expression in the spinal cord, something must produce that asymmetry in the first place. So what do you think or how do you account for the fact that you’ve got this difference in the expression of gene patterns on one side of the cord versus the other?

Sebastian - So that’s probably the biggest open questions I want to address in my research in the future, which environmental factors actually trigger these epigenetic processes. I can really say I have a good clue at that right now. Some people for example suggests stress might play a role. Some other please suggested that intrauterine hormonal environment, for example, testosterone level. But it’s really something that we will have to look up in follow up experiments. I cannot really answer that right now. I'm sorry.