Location, Location, Location: Signals in Muscle Specification

Abstract

Muscles control body movement and locomotion, posture and body position and soft tissue support. Mesoderm derived cells gives rise to 700 unique muscles in humans as a result of well-orchestrated signaling and transcriptional networks in specific time and space. Although the anatomical structure of skeletal muscles is similar, their functions and locations are specialized. This is the result of specific signaling as the embryo grows and cells migrate to form different structures and organs. As cells progress to their next state, they suppress current sequence specific transcription factors (SSTF) and construct new networks to establish new myogenic features. In this review, we provide an overview of signaling pathways and gene regulatory networks during formation of the craniofacial, cardiac, vascular, trunk, and limb skeletal muscles.

Keywords: BMP; FGF; NOTCH; RA; SHH; WNT; ephrins; mesoderm; myogenesis; sequence specific transcription factor.

Figure 1

Signaling Molecules in Myogenesis (a) Paraxial mesoderm (PM) located next to the neural tube (NT). Dorsal PM gives rise to head and pharyngeal muscles while dorsal PM gives rise to somites. Intermediate mesoderm (IM) is located between the PM and the lateral plate mesoderm (LPM). LPM gives rise to the vascular system and skeletal muscles of the abdomen pelvis and some limb muscle. NC, notochord; (b) Anterior-posterior pattern of skeletal muscle is initiated by the RA/FGF8 inhibitory network, with AR promoting the anterior muscles and FGF8 the posterior. Activation of Wnt promotes the central somites and NOTCH signaling that will support formation of the anterior and posterior somites via EPH4 and RIPPLY, respectively; (c) Segmentation of somites into dermomyotome (DM), myotome (MT) and sclerotome (SC) is the result of signaling molecules secreted from the dorsal NT (BMP, WNT1/3a), notochord (SHH), ectoderm (WNT6/11, WNT7a, BMP4), and LPM (BMP4, FGF5). DML, dorsomedial lip; VLL, Ventrolateral lip.

Figure 2

Gene Networks Involved in Muscle Specification. LacZ staining of E12.5 Pitx2^LacZ/+ mouse. Extraocular muscles (EOM) and abdominal wall muscles are specified by PITX2. Branchial arch muscles are specified by PITX2 and TBX1. Forelimb, trunk and hindlimb muscles are specified by PAX3.