Abstract
Many species that run or leap across sparsely vegetated habitats, including horses and deer, evolved the severe reduction or complete loss of foot muscles as skeletal elements elongated and digits were lost, and yet the developmental mechanisms remain unknown. Here, we report the natural loss of foot muscles in the bipedal jerboa, Jaculus jaculus. Although adults have no muscles in their feet, newborn animals have muscles that rapidly disappear soon after birth. We were surprised to find no evidence of apoptotic or necrotic cell death during stages of peak myofiber loss, countering well-supported assumptions of developmental tissue remodeling. We instead see hallmarks of muscle atrophy, including an ordered disassembly of the sarcomere associated with upregulation of the E3 ubiquitin ligases, MuRF1 and Atrogin-1. We propose that the natural loss of muscle, which remodeled foot anatomy during evolution and development, involves cellular mechanisms that are typically associated with disease or injury.
Highlights
We focus here on a representative example of distal limb muscle loss in the bipedal three-toed jerboa (Jaculus jaculus), a small laboratory rodent model for evolutionary developmental biology, to determine if evolutionary muscle loss conforms to expectations based on what was previously known about muscle cell biology
Beginning only with knowledge of adult jerboa foot anatomy, we reached evidence for a cellular mechanism of intrinsic muscle loss during neonatal development that is surprising in the context of what is known about muscle development and pathology in more traditional laboratory species
We found multinucleated myofibers in the feet of neonatal jerboas, all muscle protein expression rapidly disappears from the jerboa foot shortly after birth
Summary
Muscles in the feet of birds, reptiles, and mammals were lost multiple times in the course of limb evolution, usually coinciding with the loss of associated digits and elongation of remaining skeletal elements (Hudson, 1937; Raikow, 1987; Pavaux and Lignereux, 1995; Botelho et al, 2014; Abdala et al, 2015; Berman, 1985; Cunningham, 1883; Souza et al, 2010). A mechanism called programmed cell death is often responsible for specific tissues disappearing during development, but the experiments of Tran et al revealed that this was not the case in jerboas Instead, their intrinsic muscles were degraded by processes triggered by genes that disassemble underused muscles. The muscle masses are subdivided into individual muscle groups in response to cues from the developing muscle connective tissue, which is derived from limb field lateral plate mesoderm (Hayashi and Ozawa, 1991; Kardon, 1998; Kardon et al, 2003; Wortham, 1948) They initiate a differentiation program, which includes cell fusion to form aligned multinucleated myofibers (Abmayr and Pavlath, 2012; Kelly and Zacks, 1969). Mechanism of myofiber loss is similar to atrophy, which is typically considered a pathological response to injury or disease
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