Embryonic development depends on the precise spatial and temporal regulation of gene expression by transcription factor proteins. Understanding how transcription factors influence cell fate decisions and subsequent morphogenesis is a fundamental question of developmental biology. We use limb development in the laboratory mouse as a model system to study how transcription factors control the development of specific structures. Many transcription factors that are required to form limb elements have been identified, but we know comparatively little about how these proteins actually function. Most notably, very few of the target genes that are regulated by transcription factors during limb development have been identified. Likewise, we know little about how the expression of the transcription factor genes themselves is controlled.
To address these issues, my research program focuses on the mouse short-stature homeobox-containing gene 2 (Shox2), which we have shown is absolutely required for the development of the proximal bones of the limbs, the humerus and femur. Short-stature genes are of particular interest because mutations of the human SHOX gene cause the limb deformities found in three human syndromes. Interestingly Shox2 is the only short-stature gene in the mouse genome, while humans have two. The lack of the Shox gene in the mouse genome is especially noteworthy since virtually all other human genes involved in patterning basic embryonic structures have a single matching ortholog in the mouse. The Shox genes therefore present a unique opportunity to study how very similar structures (i.e. human and mouse limbs) can be patterned by different gene complements.