ABSTRACTOne of the decisive questions about human gross anatomy is unmatching the adult branching pattern of the spinal nerve to the embryonic lineages of the peripheral target muscles. The two principal branches in the adult anatomy, the dorsal and ventral rami of the spinal nerve, innervate the intrinsic back muscles (epaxial muscles), as well as the body wall and appendicular muscles (hypaxial muscles), respectively. However, progenitors from the dorsomedial myotome develop into the back and proximal body wall muscles (primaxial muscles) within the sclerotome-derived connective tissue environment. In contrast, those from the ventrolateral myotome develop into the distal body wall and appendicular muscles (abaxial muscles) within the lateral plate-derived connective tissue environment. Thus, the ventral rami innervate muscles that belong to two different embryonic compartments. Because strict correspondence between an embryonic compartment and its cognate innervation is a way to secure the development of functional neuronal circuits, this mismatch indicates that we may need to reconcile our current understanding of the branching pattern of the spinal nerve with regard to embryonic compartments. Accordingly, we first built a model for the branching pattern of the spinal nerve, based on the primaxial-abaxial distinction, and then validated it using mouse embryos.In our model, we hypothesized the following: 1) a single spinal nerve consists of three nerve components: primaxial compartment-responsible branches, a homologous branch to the canonical intercostal nerve bound for innervation to the abaxial compartment in the ventral body wall, and a novel class of nerves that travel along the lateral cutaneous branch to the appendicles; 2) the three nerve components are discrete only during early embryonic periods but are later modified into the elaborate adult morphology; and 3) each of the three components has its own unique morphology regarding trajectory and innervation targets. Notably, the primaxial compartment-responsible branches from the ventral rami have the same features as the dorsal rami. Under the above assumptions, our model comprehensively describes the logic for innervation patterns when facing the intricate anatomy of the spinal nerve in the human body.In transparent whole-mount specimens of embryonic mouse thoraces, the single thoracic spinal nerve in early developmental periods trifurcated into superficial, deep, and lateral cutaneous branches; however, it later resembled the adult branching pattern by contracting the superficial branch. The superficial branches remained segmental while the other two branches were free from axial restriction. Injection of a tracer into the superficial branches of the intercostal nerve labeled Lhx3-positive motoneurons in the medial portion of the medial motor column (MMCm). However, the injection into the deep branches resulted in retrograde labeling of motoneurons that expressed Oct6 in the lateral portion of the medial motor column (MMCl). Collectively, these observations on the embryonic intercostal nerve support our model that the spinal nerve consists of three distinctive components.We believe that our model provides a framework to conceptualize the innervation pattern of the spinal nerve based on the distinction of embryonic mesoderm compartments. Because such information about the spinal nerves is essential, we further anticipate that our model will provide new insights into a broad range of research fields, from basic to clinical sciences.
Dermomyotome-derived endothelial cells migrate to the dorsal aorta to support hematopoietic stem cell emergence
