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International audience; In most vertebrates, the upper digestive tract is composed of muscularized jaws linked to the esophagus that permits food ingestion and swallowing. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we show that the transcription factors Tbx1 and Isl1 are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies point to MET/HGF signaling for antero-posterior migration of esophagus muscle progenitors, where Hgf ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Our findings establish a Tbx1-Isl1-Met genetic hierarchy that uniquely regulates esophagus myogenesis and identify distinct genetic signatures that can be used as framework to interpret pathologies arising within CPM derivatives.

How dietary selection affects genome evolution to define the optimal range of nutrient intake is a poorly understood question with medical relevance. We have addressed this question by analyzing Drosophila simulans and sechellia, recently diverged species with differential diet choice. D. sechellia larvae, specialized to a nutrient scarce diet, did not survive on sugar-rich conditions, while the generalist species D. simulans was sugar tolerant. Sugar tolerance in D. simulans was a tradeoff for performance on low-energy diet and was associated with global reprogramming of metabolic gene expression. Hybridization and phenotype-based introgression revealed the genomic regions of D. simulans that were sufficient for sugar tolerance. These regions included genes that are involved in mitochondrial ribosome biogenesis and intracellular signaling, such as PPP1R15/Gadd34 and SERCA, which contributed to sugar tolerance. In conclusion, genomic variation affecting genes involved in global metabolic control defines the optimal range for dietary macronutrient composition., eLife digest Animals meet their nutritional needs in a variety of ways. Some animals are specialists feeding only on one type of food; others are generalists that can choose many different kinds of food depending on the situation. Despite these differences in diet, animals have similar needs for basic cellular metabolism. This suggests that generalist and specialist species likely process the foods they eat in different ways in order to meet their basic needs. For example, the metabolism of generalist species may be more flexible to adapt to changing food sources. To learn more about how metabolism evolves to respond to diet, scientists can study closely related species that eat different foods. For example, a species of fruit fly called Drosophila simulans is a generalist and its larvae can grow and develop by feeding on different kinds of decaying fruits and vegetables. Larvae of a closely related fruit fly called Drosophila sechellia are specialized to eat only the nutrient-poor Morinda fruit. Looking at how genetic differences between these species affect metabolism may provide scientists with clues about how these feeding strategies evolved. Melvin et al. grew larvae of D. sechellia and D. simulans in different conditions. D. sechellia larvae thrived in low nutrient conditions, but died when exposed to high sugar foods. By contrast, D. simulans larvae tolerated high sugar levels, but did poorly in low-nutrient conditions. Melvin et al. then bred the two species with each other, selecting flies that are genetically similar to D. sechellia but have the genes necessary for larvae to tolerate sugar. Analyzing the selected hybrid flies revealed genetic changes that explain the different survival abilities of each species. These changes suggest that D. sechellia rapidly evolved to thrive in low nutrient conditions, but the trade-off was losing their ability to tolerate high sugar levels. Overall, the results presented by Melvin et al. suggest that genetic adaptions to food sources can occur quickly and drastically change metabolism. Further research will be needed to confirm if similar metabolic trade-offs developed as part of human evolution. If so, human populations that survived with limited nutrition for many generations may have a harder time adapting to high-sugar modern diets.