The Genetic Roots of Bone

It starts with a well-known story: sperm meets egg and two sets of genes join. The fused cell is the precursor of all of the body’s tissues: blood, muscle, brain, bone. Each cell carries a duplicate of the original genetic tool kit, and from this kit, individual genes are turned on and off to create specific kinds of tissue. Dr. Elazar (Eli) Zelzer, a developmental biologist in the Weizmann Institute’s Molecular Genetics Department, investigates genes that are crucial to the development of bones.

Bone is one of the more curious structures in nature, formed during embryonic development from a unique material that is flexible, yet resistant to the stress of compression. Prof. Steve Weiner of the Structural Biology Department studies how in the early embryo microscopic “onion skins” of this material grow to become full-fledged bone. But where do the different genes enter the picture? Zelzer and Weiner put their heads together to check the genetic process, on the one hand, and to investigate the mechanical and physical properties of developing bone, on the other. This uncommon mix of interests and methods allows the scientists to attack the question from both ends, an approach that should bring new insights into the field.
 
To study the genetics of bones, Zelzer uses a method of selectively activating or suppressing specific genes known to affect their development. By applying this method to different gene combinations, he is able to produce a whole range of mice with different patterns of bone building, allowing him to begin tracing the complex interplay of genes involved. For instance, a gene coded for the growth of new blood vessels was found to be crucial for producing healthy bone; this gene had previously been known to stimulate the growth of blood vessels in tumors. Another gene, one for forming muscle, was found to affect bone structure when its activity was arrested.

To assess the physical effects of these genetic manipulations, Weiner, together with Prof. Asher Friesem of the Physics of Complex Systems Department, built a device that is capable of gauging the mechanical properties of tiny bone samples only one or two millimeters long, such as those from the embryonic mice. The scientists hope to use these measurements to make a direct connection between specific genes and the material properties of developing bones as well as the genetic causes of bone diseases.   

Dr. Elazar Zelzer’s research is supported by the Leo and Julia Forchheimer Center for Molecular Genetics and the Women's Health Research Center. Dr. Zelzer is the incumbent of the Martha S. Sagon Career Development Chair.

Prof. Steve Weiner’s research is supported by the Center for Scientific Excellence; the Helen and Martin Kimmel Center for Archaeological Science; the Philip M. Klutznick Fund for Research; the Alfried Krupp von Bohlen und Halbach Foundation; the Women's Health Research Center; and George Schwartzman. Prof. Weiner is the incumbent of the Dr. Walter and Dr. Trude Borchardt Professorial Chair in Structural Biology.