Genetically Linked Scientists

The comprehensive report in this issue by Ranger et al. (1) is a landmark contribution for several reasons: first, it identifies an important regulatory agent that functions in several diverse mesenchymal pathways; second, it shows that transcription factors that affect differentiation pathways in adults are not necessarily prominent in embryonic events; third, it documents that alert and inquisitive minds are most effective when their field of vision is not restricted to the narrow limit of their specialized fields; and finally, it demonstrates that collegial and scholarly networks are important in scientific inquiry. In the context of this last point, it is important to point out that although the physician–basic scientist phenotype is being squeezed by fiscal and organizational constraints and is, thus, endangered, the physician-scientists are well positioned as bridging components and are uniquely contributory to the progress of scientific inquiry. As an unusual human interest aside, a behind-the-scenes situation developed in which the molecular immunologist daughter went to her orthopedic surgeon father to help unravel the key features of an experimental system. The primary focus of these studies is the nuclear factor of activated T cells (NFAT) family of transcription factors that are regulatory components in T lymphocyte activation in adults (2, 3). Interestingly, one member of this family, NFATc, is active in the morphogenesis of cardiac valves and septum (4, 5), indicating that other members of the NFAT family could be regulators of other mesenchymal tissues. In the 1990s, one powerful way to study a family of regulatory factors is to " knock out " each gene of that family and to study the developmental and physiological consequences. Laurie H. Glim-cher's laboratory and others used this strategy (4-10) and, as might be expected, observed that the immune system of the mice was affected. Importantly, new insight into the control of the genesis of a specific class of immune cells was obtained that may have implications for organ transplanta-tion or immune deficiency diseases. In the tedious and often unrewarding process of raising, back-crossing, and breeding these knockout mice, the researchers in Glimcher's lab noticed that the older, breeding, NFATp-deficient female mice had distinctive limps and eventually developed severe ambulation problems. For a laboratory focusing on the details of immune regulation, this side-observation was bothersome but certainly not profound. This ambulation difficulty may have led to naught had Laurie Glimcher, an established T cell molecular biologist (6, 7, 11–14), not …