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Abstract

Animals interact with their environment based on stereotypical movement patterns, such as those performed during running, breathing or feeding. Hox regulatory genes had been known to be essential for establishing coordinated movements, but the molecular underpinnings of feeding behaviour were not well understood. Using Drosophila melanogaster as a model system, the present work demonstrates that a specific Hox gene, Deformed, controls the establishment of a motor unit in the fly's head during embryonic development. This unit comprises a muscle and a set of stimulating neurons and enables feeding-related movements. The loss of functional Deformed caused severe defects in the formation of the feeding motor unit and subsequently led to death. Furthermore, inactivation of Deformed at the end of embryogenesis, once the motor unit was successfully assembled, uncovered a novel role for Deformed in maintaining the functionality and integrity of the motor unit later in life. Finally, perturbations in motor behaviour were pinned to the role of Deformed in the control of molecules essential for synapse stability at the junctions between neurons and muscles. One of the identified direct targets of Deformed is Ankyrin, a molecule previously shown to be involved in neurodegenerative diseases such as Alzheimer's. Hence, the results presented here suggest that Hox genes might have a neuroprotective function and once this function is gone, the neurons degenerate, a hypothesis that will be of interest to study in the future. Interestingly, Deformed is co-expressed in muscles and neurons forming the functional feeding motor unit, pointing at its role as a master regulator of feeding behaviour. In support of this hypothesis, Deformed was shown to act as one of the negative upstream regulators of Connectin, a molecule essentially required for the correct matching between the two partners. Is the function of Hox transcription factors in the establishment of feeding motor units conserved across the animal phylogeny? This work uncovered a fly neural regulatory element of Deformed, which contains highly conserved Hox-binding sites, to be active in neurons located within the hindbrain of the vertebrate fish model Oryzias latipes, suggesting that the transcriptional network controlling the assembly and function of the feeding unit in fish and flies is conserved.