Tissue Interaction in Pharyngeal Arches
Authors: Ziermann Janine M. 
Published: May 2022

The occurrence of paired pharyngeal arches (PAs) during the embryonic development of vertebrates is an essential step for the formation of head and heart structures. In fish these arches are often called branchial arches. Each PA is very simple built. On the outside is a layer of ectodermal epithelium, on the inside a layer of endodermal epithelium, and in between is a core of mesenchyme formed by mesodermal and neural crest cells. Ectoderm will give rise to outer structures and contributes to few structures connected to the inside of the head (e.g., part of tympanic membrane in tetrapods), endodermal layer will form the lining of the foregut and contributes to formations of glands, the mesodermal cells will give rise to muscles, craniofacial skeleton, and vascularization, and the neural crest cells to craniofacial skeleton and connective tissue, among others. Each arch is associated with an arch‐specific cranial nerve (CN; e.g., PA1 – trigeminal nerve, CN V; PA2 – facial nerve, CN VII, etc.) which innervates the muscles derived from the mesoderm of the same arch. Considering that the PAs are repetitive swellings lateroventrally in the developing embryonic head region in vertebrates, it is fascinating how diverse heads (and hearts) are in these animals.Gene regulatory networks (GRNs) and communication between all tissues play a crucial role in giving each arch its own identity and during differentiation of arch specific cartilages, bones, muscles, and arteries. Well‐known examples are the distribution of homeobox genes along the antero‐posterior and dorso‐ventral axis determining the identity of PAs 1‐6 (7+ in several fishes) and their proximo‐distal orientation. PA1 is determined by Otx2, while the more posterior PAs are determined by overlap of Hox2 (PA2; Hunger & Prince 2002), Hox2 and Hox 3 (PA3), Hox2, Hox3, and Hox4 (PA4+) (Takio et al. 2007). Intrinsic to each arch is the dorso‐ventral axis which is patterned by Dlx genes with Dlx1 and Dlx2 being more dorsally expressed while Dlx5 and Dlx6 are more ventrally expressed (Qui et al. 1997). While these patterning mechanisms are important, the GRNs in the PAs and between tissues are still not well understood.Ectoderm and endoderm signal to the neural crest cells and mesodermal cells to differentiate, and the letter two tissues interact with each other to ensure differentiation in a highly coordinated manner. For example, the interaction of pharyngeal arch core expressed Pax9 and pharyngeal endoderm expressed Tbx1 controls the morphogenesis of the 4th pharyngeal arch artery (Phillips et al. 2019). Sonic hedgehog (Shh) is expressed in the pharyngeal ectoderm and endoderm and essential for the development of mandibular arch (1st PA)‐derived cartilages (jaw) (Billmyre & Klingensmith 2015). In recent years several other examples of tissue interactions were provided. Here, I aim to provide an overview of the most recent described GRNs and tissue interactions relevant for the differentiation of PA‐derived musculature and its dependence or independence on the development of cranial nerves innervating them.ReferencesBillmyre KK & Klingensmith J (2015). DevDyn 244, 564‐576.Phillips HM, et al. (2019). Development 146, dev177618.Qiu M, et al. (1997). DevBiol 185, 165‐184.Takio Y, et al. (2007). DevBiol 308, 606‐620.Trainor PA & Krumlauf R (2001). CurOpCellBiol 13, 698‐705.