Pharyngeal mesoderm development during embryogenesis: implications for both heart and head myogenesis

Abstract

The pharyngeal mesoderm (PM), located in the head region of the developing embryo, recently triggered renewed interest as the major source of cells contributing to broad regions of the heart as well as to the head musculature. What exactly is PM? In this review, we describe the anatomical and molecular characteristics of this mesodermal population and its relationship to the first and second heart fields in chick and mouse embryos. The regulatory network of transcription factors and signalling molecules that regulate PM development is also discussed. In addition, we summarize recent studies into the evolutionary origins of this tissue and its multipotential contributions to both cardiac and pharyngeal muscle progenitors.

Figure 1

Pharyngeal mesoderm cells give rise to parts of the heart and the pharyngeal muscles. (A–D) Schematic illustration of the anatomy of the pharyngeal mesoderm in sections of a 1.5–3-day-old chick embryo. Pharyngeal mesoderm cells (green) in the anterior part of the embryo surround the pharynx. Later, these cells fill the mesoderm core of the pharyngeal arches, and are incorporated into the arterial pole of the heart (e.g. outflow tract). The first heart field (pink) is restricted to the lateral splanchnic mesoderm that later contributes to the linear heart tube. Second heart field cells (green) are PM cells that contribute to the arterial pole of the heart. PM cells interact and migrate together with cranial neural crest cells. Cardiac neural crest cells are part of the cranial neural crest population, migrating into the outflow tract via the posterior arches (arches 3–6).

Figure 2

Isl1 marks pharyngeal mesoderm cells that populate the heart and the pharyngeal muscles. (A–C) Lineage studies in the chick have revealed the contribution of PM cells to the distal core of the pharyngeal arches and the heart. ISL1 protein expression is seen in this region (B–C), which is correlated with delayed differentiation of these myogenic progenitors (MYF5^-). (D–F) Similarly, lineage analyses in mouse Isl1Cre; Rosa26LacZ E10.5 embryos (D) demonstrate the significant contribution of these cells to the core of the first pharyngeal arch and the heart. The heterogenic contribution of the Isl1 lineage to the head musculature at E16.5 is shown (E–F): A section of the Isl1Cre; Rosa26YFP embryo stained for muscle (red) or GFP (green). Isl1⁺ cells contribute strongly to lower jaw muscles (yellow), muscles of facial expression shown in the head periphery, and less to jaw closing muscles (orange). Extraocular muscles (EOMs) or tongue muscles are not derived from Isl1⁺ cells. (F) A diagram of the embryonic head (lateral view) reveals the contribution of high (yellow) and intermediate levels (brown) of the Isl1 lineage to the head musculature.

Figure 3

Isl1⁺ PM cells evolved from an ancestral myogenic programme for both cardiac and skeletal muscle lineages. (A) Nematodes such as the worm C. elegans do not have a heart; instead, they have a contractile pharyngeal muscle that functions like the heart in vertebrates. (B) Tunicates (Ciona intestinalis) are chordates that are considered as a ‘sister group’ to the vertebrates. Unlike nematodes, the heart and pharyngeal muscle cells in tunicates are seemingly distinct. Isl1⁺ cells in Ciona give rise to the pharyngeal muscles (termed siphon muscles), and not to the heart. (C) Reallocation of Isl1+ PM cells into the looping heart, which occurred during evolution from chordates to vertebrates, represents the emergence of the second heart field.

Figure 4

Clonal relationships of head and heart muscle progenitors in the mouse. Schematic representation of PM cells contributing to the core of the pharyngeal arches in the mouse embryo. (A) The linear heart tube at E8.0 is aligned at the level of the first pharyngeal arch; 1–2 days later, the heart undergoes looping, and shifts posteriorly. (B) First arch PM cells (blue) migrate to the developing heart tube to contribute to right ventricular myocardium. PM cells from the second arch (pink) migrate later (around E9.5–E10), to contribute to outflow tract myocardium (oft). (C) Diagram depicting the contribution of the different lineages to head muscles and heart myocardium: The first lineage (blue) contributes to masticatory muscles (temporalis and masseter) and to right ventricular (rv) myocardium. The second lineage (pink) contributes to facial expression muscles, and to myocardium at the base of the pulmonary trunk (pt) or aorta (ao). Modified after Lescroart F et al. Adapted with permission.