Hox genes past, present and future of master regulator genes

The pioneering work of Ed Lewis, summarized in his founding paper published in Nature in 1978, forty years ago, revealed that the “homeotic” genes of the bithorax complex confer distinct identities to the different segments of the Drosophila melanogaster fruit fly. As early as 1978, it appeared that Hox genes contribute to controlling the development of all bilaterian animals and are involved in a vast repertoire of biological activities. To celebrate this seminal discovery, The International Journal of Developmental Biology decided to launch a Special Issue, and two LIBST researchers had the honor to be guest editors for this Issue.

Prof F. Gofflot and R. Rezsohazy, together with their Canadian colleague Prof. L. Jeannotte, entitled the issue “Hox genes: past, present and future of master regulator genes” since despite four decades of amazing discoveries, numerous questions remain unanswered, which open new avenues of research. The high-level reviews and original research reports collected in this issue reflect the wide-range and important topics that are still in the spotlights including the origins of Hox genes, the regulatory events controlling their expression, the mechanisms driving the action of HOX proteins, and their multiple roles in normal development and pathogenesis. It is now clear that the seminal discoveries of homeotic genes paved the way for a wealth of research and engendered a community of scientists who perpetuate the excitement of revealing the world of Hox genes and HOX proteins.

To discover these papers :  http://www.ijdb.ehu.es/web/issues/contents/vol/62/issue/11-12

Prof. Françoise Gofflot’s main project is devoted to decipher the functions and mode of actions of HOX proteins in the postnatal and adult brain. She established her own research group in 2008, and in less than 10 years, she invested a totally new niche in the field of Hox genes research. Indeed, unravelling on a systematic way the expression pattern of Hox genes in the adult brain was something no research group has initiated. Her in vivo approach to further study the functions of Hox genes in the brain is intimately connected to the understanding of their molecular modes of action, a question that is addressed in collaboration with her colleague René Rezsohazy. Combining her skills in mouse genetics and developmental neurobiology, she focused on the Hoxa5 gene, based on its specific expression pattern in the adult brain and on the availability of mouse models (from the group of Dr. Jeannotte) to tackle the specific question of Hox gene postnatal activity in the brain. In this special Issue she summarizes and discusses data suggesting that HOX transcription factors are required in postmitotic neurons for important aspects of circuit formation, namely synapse formation, focusing on the mammalian central nervous system. She also considers how new data on HOX regulatory networks could contribute to a better understanding of processes underlying synapse pathologies and neurological diseases.
Emerging roles for HOX proteins in synaptogenesis. Françoise Gofflot and Benoit Lizen. Int. J. Dev. Biol. 62: 807 - 818 (2018) doi: 10.1387/ijdb.180299fg

Prof. René Rezsohazy studies the molecular mode of action of HOX proteins since the late 90s. While the functions of HOX proteins have indeed been intensively investigated since their discovery, their mode of action has only very recently begun to be investigated in details. The Rezsohazy group contributed to identify structural determinants of the activities of HOX proteins, in particular HOXA1 and HOXA2. They addressed the functional importance of HOX-PBX partnership in vitro and in vivo. Finally, they identified and analysed HOX target enhancers. The group of Dr. Rezsohazy is the only one in the HOX research community having performed large-scale interactomic screens to identify HOX-interacting proteins in mammals (only one similar work has been carried out for another HOX protein from drosophila, by S. Bondos et al.). These studies about the molecular and cellular activities of HOX proteins significantly contributed to confirm that the HOX proteins, known as transcription factors, also fulfill non-transcriptional functions. In the special issue of The International Journal of Developmental Biology on Hox genes, Rezsohazy and colleagues review the post-translational modifications taking place to regulate the activity of HOX proteins. By comparison with other transcription factors, it appears that the regulation of HOX protein activity by such modifications is an underestimated issue René Rezsohazy has recently started to investigate in his laboratory.
Post-translational modifications of HOX proteins, an underestimated issue. Amandine Draime, Laure Bridoux, Yacine Graba and René Rezsohazy. Int. J. Dev. Biol. 62: 733 - 744 (2018) doi: 10.1387/ijdb.180178rr

 

Published on December 19, 2018