The greatest difference between mammals is size, with a 75 million-fold difference between smallest and largest. In addition, a defining feature of humans is the large evolutionary expansion of the cerebral cortex. In marked contrast to the exquisite detail in which developmental patterning has been defined in model organisms, much remains to be learnt about the developmental and evolutionary factors controlling organ and organism size.
Over the last few years we have identified seven microcephalic primordialdwarfism genes that regulate cerebral cortex volume and organism size, encoding fundamental components of cellular machinery controlling cell proliferation. We hypothesise that such genes are components of common cellular pathway(s) and that these human disorders can provide novel insights into developmental regulation of organism size.
We are using genetic, cellular and developmental studies to address this hypothesis and further define the pathogenesis of these conditions. This work will contribute to our understanding of vertebrate growth regulation and help us understand how the human brain evolved.