Coordinated development of the limb musculoskeletal system: Tendon and muscle patterning and integration with the skeleton

Abstract

Functional movement and stability of the limb depends on an organized and fully integrated musculoskeletal system composed of skeleton, muscle, and tendon. Much of our current understanding of musculoskeletal development is based on studies that focused on the development and differentiation of individual tissues. Likewise, research on patterning events have been largely limited to the primary skeletal elements and the mechanisms that regulate soft tissue patterning, the development of the connections between tissues, and their interdependent development are only beginning to be elucidated. This review will therefore highlight recent exciting discoveries in this field, with an emphasis on tendon and muscle patterning and their integrated development with the skeleton and skeletal attachments.

Mechanobiology of limb musculoskeletal development

“…60–62 This section will discuss tendon development in the context of mechanical regulation; however, an in-depth discussion of cell and molecular regulators of tendon development can be found in several recent reviews. 63–65 …”

“…[60][61][62] This section will discuss tendon development in the context of mechanical regulation; however, an in-depth discussion of cell and molecular regulators of tendon development can be found in several recent reviews. [63][64][65] In the limb bud, Scx is first expressed by limb mesoderm at E10.5, following induction of Sox9expressing prechondrogenic progenitors at E10.0. 61 At early stages (E10.5-11.5), the domains of Scx expression are closely associated with those of muscle, although Scx + and PAX3 + progenitors are completely distinct throughout all developmental stages.…”

“…61 At early stages (E10.5-11.5), the domains of Scx expression are closely associated with those of muscle, although Scx + and PAX3 + progenitors are completely distinct throughout all developmental stages. 65 Despite early induction of Scx, a characteristic tendon pattern is not apparent until E12.5, 61,62 when aligned progenitors can be observed within all segments of the limb, connecting muscle to the skeleton. [65][66][67] Generally, the stages of limb tendon development can be defined as induction (E10.5-E12.5), differentiation (E13.5), and growth (E14.5 onward).…”

“…65 Despite early induction of Scx, a characteristic tendon pattern is not apparent until E12.5, 61,62 when aligned progenitors can be observed within all segments of the limb, connecting muscle to the skeleton. [65][66][67] Generally, the stages of limb tendon development can be defined as induction (E10.5-E12.5), differentiation (E13.5), and growth (E14.5 onward). Recent studies established a new understanding of limb tendon development, in which tendons in the autopod are regulated by a separate developmental program relative to tendons in the zeugopod or styolopod.…”

Bone Surface Micro‐Topography at Craniofacial Entheses: Insights on Osteogenic Adaptation at Muscle Insertions

“…These cellular based osteological functions can produce gross shape change of bone processes through micro anatomical bone surface modeling and remodeling modulated by the loading vector (Huang, ). The osteogenic topologies observed in this study in part conformed to the proposed tension/compression loading model illustrated in Figure .…”