vesicle grows to form an optic outgrowth. Development of physical features Face and neck From the third to the eighth week the face and neck develop. Ears The inner ear, middle ear and outer ear have distinct embryological origins. Inner ear At about 22 days into development, the ectoderm on each side of the rhombencephalon thickens to form otic placodes. These placodes invaginate to form otic pits, and then otic vesicles. The otic vesicles then form ventral and dorsal components. The ventral component forms the saccule and the cochlear duct. In the sixth week of development the cochlear duct emerges and penetrates the surrounding mesenchyme, travelling in a spiral shape until it forms 2.5 turns by the end of the eighth week. The saccule is the remaining part of the ventral component. It remains connected to the cochlear duct via the narrow ductus reuniens. The dorsal component forms the utricle and semicircular canals. Middle ear The tympanic cavity and eustachian tube are derived from the first pharyngeal pouch (a cavity lined by endoderm). The distal part of the cleft, the tubotympanic recess, widens to create the tympanic cavity. The proximal part of the cleft remains narrow and creates the eustachian tube. The bones of the middle ear, the ossicles, derive from the cartilages of the pharyngeal arches. The malleus and incus derive from the cartilage of the first pharyngeal arch, whereas the stapes derives from the cartilage of the second pharyngeal arch. Outer ear The external auditory meatus develops from the dorsal portion of the first pharyngeal cleft. Six auricular hillocks, which are mesenchymal proliferations at the dorsal aspects of the first and second pharyngeal arches, form the auricle of the ear. Eyes The eyes begin to develop from the third week to the tenth week. Limbs At the end of the fourth week limb development begins. Limb buds appear on the ventrolateral aspect of the body. They consist of an outer layer of ectoderm and an inner part consisting of mesenchyme which is derived from the parietal layer of lateral plate mesoderm. Ectodermal cells at the distal end of the buds form the apical ectodermal ridge, which creates an area of rapidly proliferating mesenchymal cells known as the progress zone. Cartilage (some of which ultimately becomes bone) and muscle develop from the mesenchyme. Clinical significance Toxic exposures in the embryonic period can be the cause of major congenital malformations,