DLX6 (distal-less homeobox 6)

Abstract

DLX6 belongs to the six-member family of DLX genes characterized by a homeobox related to that found in the insect Distal-less (Dll) gene. The six DLX genes are organized as three bigenic pairs with a tail-to-tail orientation (Zerucha et al., 2000), and located on chromosomes where HOX clusters are also found (DLX5/DLX6; 7q21.3, syntenic to the HOXA cluster), (DLX1/DLX2; 2q32 syntenic to the HOXD cluster) and (DLX3/DLX4; 17q21.33 syntenic to the HOXB cluster). During embryonic development DLX genes are involved in the control of appendage and craniofacial morphogenesis and in the differentiation of reproductive organs; in the adult they play a role in bone homeostasis and in the maintenance of tissue integrity. DNA/RNA DescriptionIn contrast to DLX5, no intragenic mutations have been found for DLX6. It is considered that disruption of distant regulatory elements is most usually responsible for DLX5/DLX6-related disorders in human. Breakpoint analyses of genomic deletions and chromosomal rearrangements in the congenital split-hand/splitfoot malformation (SHFM type 1D, OMIM #220600), have shown that positional effect and disrupted regulatory elements controlling DLX5/DLX6 activity are involved in the pathogenesis of this developmental disorder (see further "dysmorphologies"). In-depth sequencing of the candidate regions has shown that the expression of DLX6 depends upon the activity of conserved regulatory elements shared with DLX5, and located both within the DLX5/DLX6 intergenic territory and outside of the locus (see Figure 1; Lango Allen et al., 2014). Furthermore these enhancers have been identified in all examined species -including in mouse where transgenic analyses have allowed the functional characterization of their tissuespecificity.

The untold stories of the speech gene, the FOXP2 cancer gene

“… FOXP2 encodes a transcription factor involved in speech and language acquisition. Growing evidence now suggests that dysregulated FOXP2 activity may also be instrumental in human oncogenesis, along the lines of other cardinal developmental transcription factors such as DLX5 and DLX6 [ 1 – 4 ]. Several FOXP familymembers are directly involved during cancer initiation, maintenance and progression in the adult [ 5 – 8 ].…”