The role of foxi family transcription factors in the development of the ear and jaw

Abstract

The mammalian outer, middle, and inner ears have different embryonic origins and evolved at different times in the vertebrate lineage. The outer ear is derived from first and second branchial arch ectoderm and mesoderm, the middle ear ossicles are derived from neural crest mesenchymal cells that invade the first and second branchial arches, whereas the inner ear and its associated vestibule-acoustic (VIIIth) ganglion are derived from the otic placode. In this chapter, we discuss recent findings in the development of these structures and describe the contributions of members of a Forkhead transcription factor family, the Foxi family to their formation. Foxi transcription factors are critical for formation of the otic placode, survival of the branchial arch neural crest, and developmental remodeling of the branchial arch ectoderm.

Keywords: Branchial arches; Craniofacial; Forkhead; Neural crest; Pharyngeal arches; Placode; Sensory organ; Transcription factors.

Figure 1. Simple schematic diagram of the auditory apparatus

The diagram shows the external ear and canal (red), the middle ear cavity (blue) and ear ossicles (yellow) and the inner ear (green), with the embryonic origins of each component.

Figure 2. Requirements for otic induction from primitive ectoderm

The figure depicts a consensus scheme of otic induction for amniotes. For each step, the necessary signaling factors for the otic pathway are shown. The alternative pathway is chosen in the absence of the specific combination of signaling and/or with additional signals. Gene expression defining tissue identity for individual steps are indicated. X represents the requirement for an inhibitor of a signaling pathway, such as BMP or Wnt inhibitors.

Figure 3. Arrangement of germ layers and neural crest cells in the branchial arches

(A) sagittal view of an embryonic day 9.5 (E9.5) mouse embryo showing branchial arches (BA) 1–3. The external surface of each arch is ectoderm. Neural crest cells (NC) in three distinct streams populate the arches. The most anterior stream contains NC from the midbrain and rhombomeres 1 and 2 from the hindbrain. Rhombomeres 3 and 5, the white regions between streams of yellow neural crest produce very few neural crest cells. (B) Schematic of a coronal section through the arches of the embryo in (A). Branchial arches consist of external ectoderm, an endodermal lining, a core of mesoderm, and neural crest cells from the midbrain and hindbrain. The boundaries of the arches are defined by points of contact between endoderm and ectoderm: the pharyngeal pouches.

Figure 4. Signaling factors from the pharyngeal ectoderm and endoderm

At embryonic day 9.5 (E9.5), four major signaling factors are secreted from the ectoderm and endoderm. Fgf8 is expressed in the ectoderm between the arches and between the mandibular and maxillary processes of BA1 and in the endoderm at the tips of the pharyngeal pouches. Shh is expressed in endoderm underlying BA2 and BA3. Edn1 is expressed in ventral arch ectoderm, endoderm underlying the mandibular process, BA2, and BA3, and in the mesoderm of each arch. Bmp4 is expressed in the ectoderm overlying the ventral domain and the maxillary process of branchial arch 1 (BA1).