The brain and the braincase, and much more, too

In our book The Mermaid's Tale, we make the point that, in thinking about how the diversity of life arose, people often place too much emphasis on evolutionary time scales compared to the more immediate timescale on which life is actually lived. We note that no two species in nature, no matter how distant or how different their genomes, are any more different than a brain and the braincase that encloses it. Yet the brain and the braincase are made with cells having the same genome, very closely related in terms of cellular descent (from the single fertilized egg), and that in fact interact extensively with each other. This figure, from a simulation done by Brian Lambert, programmer extraordinaire with our group, illustrates how signal interactions among 3 layers, an outer epithelium, a pre-bone layer of mesodermal cells, and an underlying dural layer usually thought of as the outer layer of the brain, produce the different tissues of the brain and skull.

The difference is not in the genomes in any of the cells involved in the development of the head, of course, but in the way their genomes are used. Indeed, in research that we are doing in collaboration with Joan Richtsmeier and others here, and Mimi Jabs at Albert Einstein University in New York, we are finding the intricate way in which these two structures develop through intimate interactions of cell layers that often express similar genes. It is not even clear whether the cells of the future braincase, or those of the future brain, are 'in charge' of this process, and the very concept of a pure hierarchy of control is probably most often a misperception that may derive from our broader culture, in which we do have bosses and the bossed, and natural power hierarchies.

This cooperative kind of interaction based on signaling is essential to life, indeed we would argue that life is signaling. That means that contrary to ideas since Mendel's work on peas was rediscovered in 1900, genes per se are not as much the key to life as gene usage, and also the somewhat Lamarck-like fact that cells, if not organisms, do change--in this case their gene expression and hence their differentiation and behavior, as a result of experience (their cellular context), and these changes are inherited by their descendant cells in the body of the organism.

This is not the place to go on in detail about that--it's a major part of our book. But we are triggered to discuss the subject because a new paper by Dimas et al. in Science Express ("Common Regulatory Variation Impacts Gene Expression in a Cell Type-Dependent Manner", Dimas et al., published in Science Express online, July 30, 2009), has compared regions of the genome in which variation among individuals differently control expression of genes in several different cell lines from the individuals that were tested. The findings are, first, that each cell type has its own regulatory regions distributed across the genome. This is no surprise because each cell, such as different types of blood cells, does different things and must do that via hundreds of different expressed genes. There is variation because these individuals vary, just as you and we do. But the greater variation, as with the brain and the braincase, is among very closely related cells in terms of their gene expression.

Dimas et al. also found that regulatory regions used in only one of the tested cell types tended to cause lower levels of expression, and to be farther from the genes. Why this should be, if it is a finding that holds up in future work, is anyone's guess, but may reflect some aspect of evolution related to the cell type. Another finding was that the great majority, up to around 80%, of regulation is by control elements that only affect one of the tested cell types.

So cells differentiate to make organs, and that's what makes you as an organism. Evolution leads to differences, to be sure, but at least as interesting is the way that cells act as organisms of their own, and evolve--yes, evolve in the true sense of the word--very rapidly and by cooperative communication, rather than competition, among each other. In fact, in the book we call the developmental process of cellular differentiation cytospeciation.

These issues are important far beyond their basic interest. For example, the whole idea of using stem cells to develop replacement tissue as therapy for diseases depends on making the same starting cells become different, a singular challenge. Indeed, it's less of a challenge to produce a whole new animal with stem cells than to direct the differentiation of the cell types needed to make a single organ. But, the more this can be done with the patient's own genome, the more likely it will work.

But, some day it may be possible to take your adult skin cells, and turn them into brain or braincase, to repair damage acquired during life.