I can get lost in the exhibits and drawers of a natural history museum, and to me the skeletons are the best part. It’s fascinating that different species are so easily recognized by the isolated bones that are left behind when the natural processes of decomposition and fossilization are complete. One can’t help wonder how the dolphin turned an arm into a flipper, how the aye-aye got its creepy long finger, and how the horse evolved to run gracefully on a single toe.
Decades of research in the mouse and chick model systems as well as analyses of human birth defects have unlocked some of the mysteries of how the limb skeleton is patterned along three coordinate axes from the shoulder to finger tips, thumb to pinky finger, and back of the hand to palm. Yet neither human syndromes, nor the sledgehammer approach to knocking out genes in the mouse replicate the extraordinary range of adaptive morphologies observed in diverse species. This suggests a vast and untapped source of information about limb development and plasticity exists in the 400 million year genetic experiment that’s been continuing since the first “fishapod” flopped onto land.
To gain a window into what evolution tells us about the developmental potential of the limb, we primarily focus on the three-toed jerboa, a small bipedal rodent that is closely related to the laboratory mouse and amenable to rearing in captivity. Compared to its quadrupedal relative, the jerboa has greatly elongated hindlimbs with three toes and metatarsals that fuse into a single bone. The unusual morphology of the jerboa skeleton allows us to ask what keeps one bone from growing into its adjacent neighbor? What mechanisms determine skeletal size and the relative proportions of individual elements? How are the correct numbers and positions of the digits established, and are the same mechanisms of digit loss redeployed in species that converge on similar morphologies (i.e. jerboas and horses, pigs and camels)? How can the forelimb and hindlimb evolve independently when both utilize the same developmental pathways? We apply classical embryology, cell biology, quantitative microscopy, high throughput sequence analysis, and mouse genetics in an integrative approach to understand these developmental mechanisms at the tissue and genome level.
Kimberly Cooper completed her PhD at the Fred Hutchinson Cancer Research Center in Seattle, WA. She then carried out her postdoctoral studies in the Department of Genetics at Harvard Medical School. She joined the Division of Biological Sciences faculty at U.C. San Diego in November 2013.