Understanding Lens Development

Despite being a topic of research for one hundred years, the mechanism of lens development has remained relatively elusive. However, published in the May 15th issue of Genes & Development, Dr. Kondoh and colleagues detail their discovery that the protein, Pax6, initiates chick lens development through a coordinated effort with another well-known gene regulator.

Pax6 has previously been implicated in lens development. Vertebrate animals completely deficient in Pax6 fail to develop eyes. Partial deficiency of Pax6 in humans causes the disease aniridia. In prior work, Dr. Kondoh and colleagues identified the gene regulator, Sox2, as a necessary component of the molecular machinery that drives normal lens development. It is in this paper that Dr. Kondoh and colleagues synthesize the action of these two transcription factors.

Dr. Kondoh and colleagues determined that Pax6 binds Sox2 on a specific sequence of a lens-specific crystallin gene. By doing so, Pax6 and Sox2 activate this crystallin gene and initiate lens development. Dr. Kondoh showed that when Pax6 and Sox2 are introduced into non-eye fated cells, they activate expression of the endogenous crystallin gene and initiate lens differentiation.

This finding reveals a novel cooperation between two distinct classes of transcription factors in the regulation of specific gene expression. Pax6 is one member of a large family of structurally related transcription factors that play integral roles in maintaining normal embryonic development. Sox2 is a member of a different, but equally important, family of gene activators that are involved in a variety of developmental processes such as sex determination, cartilage formation, and lymphocyte differentiation. This discovery of coordinated Pax6/Sox2 action introduces the possibility of further Pax/Sox protein interactions in the regulation of other developmental pathways.