Self-regulated Pax gene expression and modulation by the TGFbeta superfamily

The mammalian Pax gene family encode a set of paired-domain transcription factors which play essential roles in regulating proliferation, differentiation, apoptosis, cell migration, and stem-cell maintenance. Pax gene expression is necessarily tightly controlled and is associated with the demarcation of boundaries during tissue development and specification. Auto- and inter-regulation are mechanisms frequently employed to achieve precise control of Pax expression domains in a variety of tissues including the eye, central nervous system, kidney, pancreas, skeletal system, muscle, tooth, and thymus. Furthermore, aberrant Pax expression is linked to several diseases and causally associated with certain tumors. An increasing number of studies also relate patterns of Pax expression to signaling by members of the TGFbeta superfamily and, in some instances, this is due to disruption of Pax gene auto-regulation. Here, we review the current evidence highlighting functional and mechanistic overlap between TGFbeta signaling and Pax-mediated gene transcription. We conclude that self-regulation of Pax gene expression coupled with modulation by the TGFbeta superfamily represents a signaling axis that is frequently employed during development and disease to drive normal tissue growth, differentiation and homeostasis.