RESUMEN
Neurofibromatosis type 1 is a monogenetic disorder that predisposes individuals to tumor formation and cognitive and behavioral symptoms. The neuronal circuitry and developmental events underlying these neurological symptoms are unknown. To better understand how mutations of the underlying gene (NF1) drive behavioral alterations, we have examined grooming in the Drosophila neurofibromatosis 1 model. Mutations of the fly NF1 ortholog drive excessive grooming, and increased grooming was observed in adults when Nf1 was knocked down during development. Furthermore, intact Nf1 Ras GAP-related domain signaling was required to maintain normal grooming. The requirement for Nf1 was distributed across neuronal circuits, which were additive when targeted in parallel, rather than mapping to discrete microcircuits. Overall, these data suggest that broadly-distributed alterations in neuronal function during development, requiring intact Ras signaling, drive key Nf1-mediated behavioral alterations. Thus, global developmental alterations in brain circuits/systems function may contribute to behavioral phenotypes in neurofibromatosis type 1.
Asunto(s)
Proteínas de Drosophila/genética , Desarrollo Embrionario/genética , Proteínas del Tejido Nervioso/genética , Neurofibromatosis 1/genética , Neuronas/metabolismo , Proteínas Activadoras de ras GTPasa/genética , Animales , Cognición/fisiología , Modelos Animales de Enfermedad , Drosophila melanogaster/genética , Embrión no Mamífero , Técnicas de Silenciamiento del Gen , Aseo Animal/fisiología , Humanos , Mutación/genética , Neurofibromatosis 1/patología , Neuronas/patologíaRESUMEN
Collective motion emerges from individual interactions which produce group-wide patterns in behavior. While adaptive changes to collective motion are observed across animal species, how local interactions change when these collective behaviors evolve is poorly understood. Here, we use the Mexican tetra, Astyanax mexicanus, which exists as a schooling surface form and a non-schooling cave form, to study differences in how fish alter their swimming in response to neighbors across ontogeny and between evolutionarily diverged populations. We find that surface fish undergo a transition to schooling mediated by changes in the way fish modulate speed and turning relative to neighbors. This transition begins with the tendency to align to neighbors emerging by 28 days post-fertilization and ends with the emergence of robust attraction by 70 days post-fertilization. Cavefish exhibit neither alignment nor attraction at any stage of development. These results reveal how evolution alters local interactions to produce striking differences in collective behavior.
RESUMEN
Collective motion emerges from individual interactions which produce groupwide patterns in behavior. While adaptive changes to collective motion are observed across animal species, how local interactions change when these collective behaviors evolve is poorly understood. Here, we use the Mexican tetra, A. mexicanus, which exists as a schooling surface form and a non-schooling cave form, to study differences in how fish alter their swimming in response to neighbors across ontogeny and between evolutionarily diverged populations. We find that surface fish undergo a transition to schooling during development that occurs through increases in inter-individual alignment and attraction mediated by changes in the way fish modulate speed and turning relative to neighbors. Cavefish, which have evolved loss of schooling, exhibit neither of these schooling-promoting interactions at any stage of development. These results reveal how evolution alters local interaction rules to produce striking differences in collective behavior.
RESUMEN
Reduction or complete loss of traits is a common occurrence throughout evolutionary history. In spite of this, numerous questions remain about why and how trait loss has occurred. Cave animals are an excellent system in which these questions can be answered, as multiple traits, including eyes and pigmentation, have been repeatedly reduced or lost across populations of cave species. This review focuses on how the blind Mexican cavefish, Astyanax mexicanus, has been used as a model system for examining the developmental, genetic, and evolutionary mechanisms that underlie eye regression in cave animals. We focus on multiple aspects of how eye regression evolved in A. mexicanus, including the developmental and genetic pathways that contribute to eye regression, the effects of the evolution of eye regression on other traits that have also evolved in A. mexicanus, and the evolutionary forces contributing to eye regression. We also discuss what is known about the repeated evolution of eye regression, both across populations of A. mexicanus cavefish and across cave animals more generally. Finally, we offer perspectives on how cavefish can be used in the future to further elucidate mechanisms underlying trait loss using tools and resources that have recently become available.