While forelimb length is just one of several key morphological changes that occurred during the evolution of the bat wing, this unprecedented finding demonstrates that evolution can be driven by changes in the patterns of gene expression, rather than solely by changes in the genes, themselves.

Prx1 is a paired-box homeodomain transcription factor, with an established role in limb bone growth. Dr. Behringer and colleagues identified a conserved Prx1 enhancer domain, which regulates expression of Prx1 in the developing forelimb.

To study the evolutionary contribution of the Prx1 enhancer to the morphological differences between the bat and mouse forelimb, Dr. Behringer and colleagues replaced the endogenous mouse Prx1 enhancer with that of the bat. The transgenic mice showed higher expression levels of Prx1 in the perichondrium, increased chondrocyte proliferation, and ultimately, longer forelimbs.

Dr. Behringer describes the significance of his finding as such: Darwin suggested that "successive slight modifications" would ultimately result in the evolution of diverse limb morphologies, like a hand, wing, or fin. The genetic change we engineered in mice may be one of those "slight modifications" to evolve a mammalian wing.

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Hydroxyurea is the only FDA-approved treatment specifically for the disease. Other drugs can help symptoms and complications of the disease. Bone marrow transplantation can be curative.

Sickle cell disease causes both acute (rapid, severe, short-term) and chronic (long-lasting) pain. In sickle cell disease, the acute pain episodes are called crises. Previous studies of sickle cell pain have focused on crises.

In the current study, over half of the sickle cell disease patients completing up to six months of pain diaries reported having pain on a majority of days. Almost one-third had pain nearly every day.

I believe that this study could change the way people view the pain of the disease. It is a chronic pain syndrome, said Dr. Smith. And the study results have implications for medical care, and research. We need more drugs to prevent the underlying processes that cause pain in this disease. And we need better treatments to reduce the chronic pain and suffering that these patients go through.

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