originates from a different germ layer: the ectoderm, endoderm and mesenchyme. Inner ear After implantation, around the second to third week the developing embryo consists of three layers: endoderm, mesoderm and ectoderm. The first part of the ear to develop is the inner ear, which begins to form from the ectoderm around the 22nd day of the embryo's development. Specifically, the inner ear derives from two thickenings called otic placodes on either side of the head. Each otic placode recedes below the ectoderm, forms an otic pit and then an otic vesicle. This entire mass will eventually become surrounded by mesenchyme to form the bony labyrinth. Around the 33rd day of development, the vesicles begin to differentiate. Closer to the back of the embryo, they form what will become the utricle and semicircular canals. Closer to the front of the embryo, the vesicles differentiate into a rudimentary saccule, which will eventually become the saccule and cochlea. Part of the saccule will eventually give rise and connect to the cochlear duct. This duct appears approximately during the sixth week and connects to the saccule through the ductus reuniens. As the cochlear duct's mesenchyme begins to differentiate, three cavities are formed: the scala vestibuli, the scala tympani and the scala media. Both the scala vestibuli and the scala tympani contain an extracellular fluid called perilymph. The scala media contains endolymph. A set of membranes called the vestibular membrane and the basilar membrane develop to separate the cochlear duct from the vestibular duct and the tympanic duct, respectively. Parts of the otic vesicle in turn form the vestibulocochlear nerve. These form bipolar neurons which supply sensation to parts of the inner ear (namely the sensory parts of the semicircular canals, macular of the utricle and saccule, and organ of Corti). The nerve begins to form around the 28th day. Molecular regulation Most of the genes responsible for the regulation of inner ear formation and its morphogenesis are members of the homeobox gene family such as Pax, Msx and Otx homeobox genes. The development of inner ear structures such as the cochlea is regulated by Dlx5/Dlx6, Otx1/Otx2 and Pax2, which in turn are controlled by the master gene Shh. Shh is secreted by the notochord. Middle ear The middle ear and its components develop from the first and second pharyngeal arches. The tympanic cavity and auditory tube develop from the first part of the