Abstract
BackgroundDlx5 and Dlx6 stimulate differentiation of diverse progenitors during embryonic development. Their actions as pro-differentiation transcription factors includes the up-regulation of differentiation markers but the extent to which differentiation may also be stimulated by regulation of the cell cycle has not been addressed.ResultsWe document that expression of Dlx5 and Dlx6 antagonizes cell proliferation in a variety of cell types without inducing apoptosis or promoting cell cycle exit. Rather, a variety of evidence indicates that elevated Dlx5 and Dlx6 expression reduces the proportion of cells in S phase and affects the length of the cell cycle.ConclusionsAntagonism of S-phase entry by Dlx5 and Dlx6 proteins likely represents a lineage-independent function to effect Dlx-mediated differentiation in multiple progenitor cell types.
Highlights
Dlx5 and Dlx6 stimulate differentiation of diverse progenitors during embryonic development
To test the sufficiency of Dlx5 and Dlx6 to antagonize cell division and the generality of this effect we initially tested cell populations that are not known to differentiate in response to endogenous Dlx gene expression
While a large body of literature has documented their roles in promoting differentiation of various cell types through the up-regulation of differentiation markers, the potential of Dlx genes to promote differentiation by antagonizing the cell cycle has not been addressed
Summary
Dlx and Dlx stimulate differentiation of diverse progenitors during embryonic development. Their actions as pro-differentiation transcription factors includes the up-regulation of differentiation markers but the extent to which differentiation may be stimulated by regulation of the cell cycle has not been addressed. Results: We document that expression of Dlx and Dlx antagonizes cell proliferation in a variety of cell types without inducing apoptosis or promoting cell cycle exit. A variety of evidence indicates that elevated Dlx and Dlx expression reduces the proportion of cells in S phase and affects the length of the cell cycle. The importance of the time spent in G1 for differentiation has been demonstrated by experimental manipulation of CDK activity; an artificially lengthened G1 phase is sufficient to induce neuronal differentiation [8]. A number of cell type-specific transcription factors are known to promote cellular differentiation, at least in part, by directly controlling the Vertebrate Dlx genes constitute a family of cell-type specific transcription factors that promote the differentiation of a variety of very different cell types including
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