IRCM Researchers

2. HOX transcription factors and chromatin accessibility.
How cells acquire distinct fate during embryonic development is a central question in developmental biology. Studies aimed at understanding mechanisms underlying the switch from progenitor to differentiated cells uncovered the existence of transcription factors (TFs) able to trigger chromatin accessibility. These particular TFs, referred to as pioneer factors, induce the activity of transcriptional enhancers and genes by making them accessible to other TFs and the transcriptional machinery. Our work on HOXA13 and HOXD13 transcriptional activity in developing limb provided evidence that these two TFs are required for the transition from the early limb developmental program to the late/distal program (Sheth et al., Cell Reports 2016). Our latest data show that chromatin accessibility at a series of enhancers controlling genes associated with digit development/patterning requires HOX13 function, eventually allowing other HOX factors to bind these enhancers (Desanlis et al., Nature Communications 2020). To what extent this ‘pioneering’ activity is shared by other HOX transcription factors and how the HOX13-dependent chromatin accessibility is achieved are questions being currently investigated in the lab.

3. Hox genes and morphological novelties.
Morphological diversity among animals and its adaptive advantage associated to habitats is fascinating. Such diversity is associated with modulations of developmental gene regulation and function. We use the emergence of digits, which characterizes the fin-to-limb transition, as a model system to gain further insights into changes in the regulation and function of Hox genes in the context of the emergence of novel morphological traits during evolution. For instance, our study on Hoxa11 regulation revealed that the change in Hoxa11 regulation that distinguish fish from limbed-vertebrates, is associated with the pentadactyl state (five digits per limb) of most modern limbed-vertebrates and likely underlies the transition from polydactyly (more than five digits per limb) in our ancestors, to pentadactyly (Kherdjemil et al., Nature 2016).