Understanding the Dlx-mediated effects on cell proliferation

Abstract

Dlx5 and Dlx6 are members of the Distal-less homeobox (Dlx) gene family and encode transcription factors essential for craniofacial patterning and differentiation of mineralizing cell types in the skeleton during development. Forced expression of Dlx5 or Dlx6 in progenitor cells promotes their differentiation and suppresses proliferation in vitro and in vivo. Conversely, studies involving cancer cell lines have shown that Dlx5 can promote proliferation, perhaps via direct transcriptional activation of cell cycle regulatory genes like c-Myc. We have shown that Dlx5 and Dlx6 inhibit cell growth in multipotent progenitor cells and primary limb bud cells and modestly upregulate c-Myc reporter transcription in such cells. Cumulative EdU-incorporation assays indicate that Dlx5 and Dlx6 decrease the proportion of actively cycling cells in a population and may increase the length of the cell cycle. Flow cytometry results suggest a higher proportion of cells in G1 compared to controls.