Eye and Ear Embryology PDF

Eye and ear embryology CU: Animal Body Function VIII Alexandre Trindade, PhD Placodes and Neural crest Cladogram showing phylogeny of the Chordata. Some synapomorphies of the main groups are provided in the boxes below the cladogram. A major feature of craniates is the development of a “true” he...

Eye and ear embryology CU: Animal Body Function VIII Alexandre Trindade, PhD Placodes and Neural crest Cladogram showing phylogeny of the Chordata. Some synapomorphies of the main groups are provided in the boxes below the cladogram. A major feature of craniates is the development of a “true” head: - Brain - Sensory organs The brain of craniates is tripartite, with three main primary subdivisions; and the specialized sense organs—eyes, ears, and nose—are complex. These structures are protected and supported by a bony or cartilaginous cranium or braincase. Neural crest and placodes are key innovations of the craniate/vertebrate clade. These cells arise within the dorsal ectoderm of all vertebrate embryos and have the developmental potential to form many of the morphological novelties within the vertebrate head. It is essential that neural crest and placodes associate together throughout embryonic development to coordinate the emergence of several features in the head, including almost all of the cranial peripheral sensory nervous system and organs of special sense. Development of the neural crest and placodes, near the midline of the back. In vertebrates, double-walled folds form at the anterior and lateral regions of the neural plate, the inner walls of which give rise to the neural crest while the lateral folds give rise to the neurogenic placodes. The neural crest is a transitory embryonic stem cell population that delaminates from the neural tube, undergoes an epithelial-to-mesenchyme transition (EMT), and then embarks on long-distance migrations throughout the head and trunk. Model for canonical cellular EMT and delamination program to initiate neural crest migration. Scanning electron micrograph done after peeling off the superficial ectoderm. The emigrating trunk neural crest cells are highlighted in purple. NNE: non-neural ectoderm. NT: trunk neural tube, NO: notochord, SO: somite, EN: endoderm, UPM: unsegmented paraxial mesoderm, NCC: neural crest cells. Neural crest gives rise to diverse tissues and structures throughout the vertebrate head and trunk, including much of the cartilage and bone of the craniofacial skeleton, melanocytes, many of the sensory neurons and glia of the peripheral nervous system, endocrine cells, as well as tooth and heart primordia. The major part of the vertebrate skull originates from the Neural Crest. Lateral views of the chondrocranium in avian embryo and newborn mouse. Neural crest (light blue) versus mesoderm (orange). Placodes arise as localized thickenings of ectoderm (cuboidal to columnar) that in turn give rise to cells that make up many of the sensory components in the vertebrate head: - cranial ganglia - organs of special sense Placodes can be divided into: - sensory placodes, which contribute to the eye, ear, lateral line, and olfactory organs - neurogenic placodes, which contribute sensory neurons to cranial ganglia. - Fish and amphibians possess an additional placode, known as the lateral line, involved in the mechanosensory detection of water movements and electric fields. - Some amphibian species appear to have retained a primitive form of sensory placode known as the hypobranchial placode. Development of the eye The eye is an organ of remarkable complexity and apparently flawless design. Eyes develop from three sources: (1) the neuroectoderm of the forebrain, (2) the surface ectoderm of the head, and (3) head mesenchyme of neural crest origin between these layers. Ectodermal evagination from the brain gives rise to the retina, iris and optic nerve. Invagination of surface ectoderm forms the lens. The surrounding mesenchyme forms the vascular and fibrous coats of the eye and the vitreous. During early vertebrate development, the eye field is established at the boundary between the telencephalon (brown) and the diencephalon (green) region of the forebrain. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups Blebs from the forebrain form optic grooves. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups With closure of the neural tube, these grooves expand as outpockets of the diencephalon – the optic vesicles. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups When the optic vesicles come into contact with the overlying ectoderm they trigger the initiation of the lens placode (a thickening of ectoderm) The optic vesicle remains attached to the diencephalon by an optic stalk. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups The lens placode induces the optic vesicle to invaginate and form an optic cup while the placode invaginates as well and invades the concavity of the optic cup; Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups The placode invaginates to form a lens vesicle that invades the concavity of the optic cup. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups An optic fissure is formed by invagination of the ventral surface of the optic cup and optic stalk, and a hyaloid artery invades the fissure to reach the lens vesicle Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups The primary optic vesicle becomes a double walled optic cup. With continued invagination the original lumen of the optic vesicle is reduced to a slit between: 1) inner neural retina layer 2) outer pigmented layer of the retina. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups The sensory pathway develops on the posterior 4/5 of the retina, as neuroectodermal cells proliferate and differentiate. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups The sensory pathway of the retina consists of a chain of three neurons: - Outer nuclear layer, consisting of light- or photoreceptor, either a rod cell or a cone cell. - Inner nuclear layer, consisting of amacrine, horizontal, Muller and bipolar neurons. - Ganglion cell layer, containing the ganglion cells.  1: Lens; 2: Choroid fissure; 2′: Closed choroid fissure; 3: Optic stalk; 3′: N. opticus; 4: Lumen of optic vesicle; 5: Inner layer of the optic stalk; 5′: Axons of the N. opticus; 6: Outer layer of the optic stalk; 7: Mesenchyme; 8: Central retinal artery and vein; 9: Pia and arachnoid layer of the nerve. Axons from the ganglion cells grow along the innermost layer of the retina towards and into the optic stalk, following molecular cues. Later, optic stalk forms optic nerve, whereas hyaloid vessels form the central artery and vein of retina. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups The anterior 1/5 of the optic cup is the precursor to the iris and ciliary body, that form by an extension process of neuroectoderm and neural crest cell invasion. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups The inner and outer layers of the anterior rim of the optic cup, induced by surrounding mesenchymal development, give rise to the posterior and anterior portions of iris epithelium respectively. The intrinsic muscles of the iris (sphincter pupillae and dilator pupillae) are derived from the surrounding neuroectoderm. Neuroectoderm of the Diencephalon ß Optic Grooves ß Optic Vesicles ß Optic Cups The ciliary muscle, the structure eventually responsible for changing the shape of the mature lens, is derived from invading neural crest cells. Neural crest cells also produce the stroma of the iris, which, based on its eventual concentration of melanocytes, is the largest determinant of the mature iris color. Formation of the lens A. Formation of lens placodes from surface ectoderm. B and C. Stages in the invagination of the lens placodes leading to formation of the lens vesicle. D. Separation of the lens vesicle from the surface ectoderm. E. Elongation of cells in the posterior wall of the lens vesicle. F. Elimination of the cavity within the developing lens. Formation of the lens These elongated epithelial cells loose their nuclei and become the primary lens fibres. The primary lens fibers collectively form the embryonic nucleus. Formation of the lens These elongated epithelial cells loose their nuclei and become the primary lens fibres. The primary lens fibers collectively form the embryonic nucleus. Lens fibers are transparent due to the expression of ordered crystalline proteins Formation of the lens Subsequently, secondary lens fibers begin to elongate from the lens epithelial cells to form the fetal nucleus during the gestation period and continue to grow multiple layers throughout life (slowly). The secondary lens fibers eventually grow to form the adult nucleus with new layers of lens fibers forming the lenticular cortex. During lenticular development, the hyaloid artery delivers nutrition and growth factors through the tunica vasculosa lentis, a vascular structure that envelopes the lens nucleus. However, this structure undergoes involution prior to birth to resemble the avascular lens seen in the adult. The more proximal part of the hyaloid arterial systems persists as the central artery of the retina. The vitreous is primarily composed of a gel-like substance called vitreous humor, and is a mesenchymal (NCC) derivative. The developmental progression of the vitreous can be thought of as a succession of three distinct phases. The first phase, termed the primary vitreous function to house the hyaloid vasculature as it provides nourishment to the developing anterior segment. As the primary vitreous and hyaloid vasculature regress, they are succeeded by the acellular, avascular secondary vitreous, produced by the Muller cells of the retina, which ultimately forms the bulk of what is thought of as the mature vitreous. The degeneration of the distal hyaloid vessels in the vitreous body leaves a remnant known as the hyaloid canal. The tertiary vitreous is secreted by the ciliary epithelium. Bundles of fibers extend from the ciliary epithelium toward the lens equator, covering the secondary vitreous anteriorly. In the adult they persist as lens zonular fibers (suspensory ligament of the lens). The anterior chamber of the eye develops from a cleft-like space within the mesenchyme between the developing cornea and the lens. The posterior chamber of the eye arises from a space that forms in the mesenchyme posterior to the developing iris and anterior to the developing lens. Anterior and posterior chambers of the eye can communicate with each other through the pupil opening. The anterior and posterior chambers are filled with aqueous humour, which is secreted into the posterior chamber by the epithelial cells (of neuroectodermal origin) of the ciliary body.  LV – Lens vesicle Me – Mesenchymal cells SE – Surface epithelium Re – Neural retina PE – Retinal pigmented epithelium EF – Embryonic choroidal fissure HA – Hyaloid artery L – Lens Mesenchyme from neural crest around the optic vesicle will contribute to: - the fibrous coat of the eye (sclera/cornea) externally - the choroid (vascular) layer adjacent to the pigment layer. The mature cornea is composed of three layers: - epithelium, - stroma, - endothelium Each layer has distinct embryologic origins: - The corneal epithelium is a derivative of surface ectoderm proximal to the developing lens. - The corneal stroma and endothelium, and other structures are derived from successive waves of invading neural crest cells. The mature, transparent cornea is ultimately formed when the mesenchymal-derived stromal keratocytes produce a highly organized stromal collagen matrix. The eyelids begin to form from contributions of both neural crest-infiltrated mesenchyme and nearby surface ectoderm. Two distinct eyelid folds become apparent, and epithelial cells begin to invaginate in the area of the medial lid margins. The upper and lower lids proceed to refuse via epithelial cell migration and proliferation. Adhesion of the eyelids is a temporary union as they separate again before or shortly after birth. The space between the fused eyelids and the cornea is called the conjunctival sac. In domestic animals, a fold of mesenchyme covered by conjunctiva develops into the third eyelid (nictitating membrane). Later, within the mesenchymal tissue, a cartilage forms that gives rigidity to the third eyelid. The lacrimal gland develops from epithelial proliferations of the conjunctival sac which fuse and give rise to a glandular structure with acini and ducts. Superficial rod‐like cords of ectoderm extend from the medial canthi of the eyelids to the developing nasal pits which are the primordia of the nasal cavities. These cords become canalised forming the membranous naso‐lacrimal duct. The lacrimal glands and their associated duct systems constitute the lacrimal apparatus. https://www.youtube.com/watch?v=ghHDFWlfpoQ Clinical considerations: The ungulate retina is mature at birth, but the carnivore retina does not fully mature until about 5 weeks postnatally. Retinal detachment occurs between the neural and outer pigmented layers of the retina (inner and outer walls of the optic cup) which do not fuse but are held apposed by pressure of the vitreous body. Coloboma is a defect due to failure of the optic fissure to close. Microphthalmia (small eye) results from failure of the vitreous body to exert sufficient pressure for growth, often because a coloboma allowed vitreous material to escape. Persistent pupillary membrane results when the pupillary membrane fails to degenerate and produce a pupil. The surface ectoderm gives rise to the lens, the lacrimal gland, the epithelium of the cornea, conjunctiva, and adnexal glands, and the epidermis of the eyelids. The neural crest, which arises from the surface ectoderm in the region immediately adjacent to the neural folds of neural ectoderm, is responsible for formation of the corneal keratocytes, the endothelium of the cornea and the trabecular meshwork, the stroma of the iris and choroid, the ciliary muscle, the fibroblasts of the sclera, the vitreous, and the optic nerve meninges. It is also involved in formation of the orbital cartilage and bone, the orbital connective tissues and nerves, the extraocular muscles, and the subepidermal layers of the eyelids. The neural ectoderm gives rise to the optic vesicle and optic cup and is thus responsible for the formation of the retina and retinal pigment epithelium, the pigmented and nonpigmented layers of ciliary epithelium, the posterior epithelium, the dilator and sphincter muscles of the iris, and the optic nerve fibers and glia. The mesoderm is now thought to contribute only to the extraocular muscles and the orbital and ocular vascular endothelium. Development of the ear The ear is the special sensory organ of the body associated with hearing and equilibrium in vertebrates. The external ear, which directs sound towards the middle ear, is formed from the first pharyngeal cleft and its surrounding mesenchyme. This part of the ear consists of the auricle, the external auditory meatus and the outer lining of the tympanic membrane. The middle ear, which conducts and amplifies sound from the external to the inner ear, is derived from the first pharyngeal pouch and its surrounding mesenchyme. This segment of the ear is composed of the auditory tube, the tympanic cavity and its associated auditory ossicles. The inner ear, also referred to as the vestibulocochlear organ, includes the utricle, the semicircular ducts, the saccule and the cochlear duct. This subdivision of the ear develops from the otic placode. The vestibular apparatus is the sensory transducer for balance, while the cochlear apparatus contains auditory sensory receptors. The inner ear begins to form as an otic placode (a thickening) in the ectoderm, and invaginates as the otic pit. The otic pit becomes internalised as the otic vesicle (otocyst). The early otic vesicle is characterized as having broad competence and can be subdivided into: - sensory, - non-sensory, - neurogenic components. Prosensory sub-domain gives rise to the support cells and hair cells. Neurogenic sub-domain gives rise to the auditory neurons and vestibular neurons. During the formation of the otic vesicle, individual neuroblasts delaminate from its anteroventral region (from neurogenic sub-domain) and coalesce to form the vestibulochochlear ganglia of cranial nerve VIIIth. The remaining cells of the otocyst will form the membranous labyrinth (vestibule and cochlear) The middle part of the otic vesicle develops into the endolymphatic duct and sac. The pars superior gives rise to the three semicircular canals and the utricle. The pars inferior of the otic vesicle gives rise to the saccule and coils to form the cochlear duct. The utricle becomes separated from saccule by a small duct, the utriculosaccular duct. The cochlear duct elongates from the saccule and undergoes coiling. How much elongation and how many turns it forms are species-specific. A connection of the cochlea with the saccule, the ductus reuniens, is also formed. Morphogenesis of the mouse inner ear over a seven-day period in embryogenesis, revealed by filling of the cavity of the developing otocyst with opaque paint. The Typical Form of the Cochlea and its Variations. Henky J.Watt. 1916 Three disc like diverticula grow out from the utricular parts of the primordial membranous labyrinths. The central portion of these undergoes apoptosis and form the semicircular ducts. Dilations at the end of each semi- circular duct, referred to as ampullae, contain the sensory organs of balance. - A canal pouch forms by thinning of the otic epithelium. - Cell division in surrounding mesenchyme (shown as ∞∞) pushes the sides of the pouch together - Cells adhere, fuse and resolve at a fusion plate. - Cells are cleared in this area by apoptosis (shown as xx). As the otic vesicle develops, it becomes filled with endolymph, a specialised extracellular fluid. The otocyst is surrounded by and closely apposed to mesenchyme of mesodermal and neural crest origin, called periotic mesenchyme. The otocyst instructs localized condensation of periotic mesenchyme and formation of a fully chondrified otic capsule, that later ossifies to form the bony labyrinth (otic capsule). Sequential stages in the formation of the structures of the cochlea: A. Cochlear duct surrounded by periotic mesenchyme. B. The inner lining of this cartilaginous shell undergoes vacuolation, resulting in a space between the outer shell of the cartilaginous and membranous labyrinth, the perilymphatic space: - scala tympani - scala vestibuli C. Spiral ganglion cells from the wall of the cochlear duct migrate to form the spiral ganglion. The cochlear duct is the only part of the cochlea that is derived from the otocyst. The cochlear duct is transformed into the Organ of Corti by differentiation of the prosensory sub-domain into hair cells (mechanotransducer cells) and support cells. The organ of Corti is a specialized sensory epithelium that allows for the transduction of sound vibrations into neural signals. The same process of vacuolation of the cartilaginous shell happens throughout the membranous labyrinth. The membranous labyrinth becomes suspended in perilymph, inside the perilymphatic space. The differentiation of sensory Hair cells in the vestibular structures occurs by similar mechanisms to what happens in the cochlea. Each of these structures has a prosensory sub-domain that is regulated by Notch signaling to differentiate Hair cells. Otoliths (otoconia) are the biomineralised ‘ear stones’ that sit above vestibular hair cells of the saccule and utricle, enabling the detection of gravity and linear acceleration. Otolith precursor particles tether to the tips of the kinocilia of the first hair cells (tether cells) in the ear, in a process defined as otolith seeding. Otolith are seeded across the lumen above the sensory epithelium of the utricle and saccule. A seed has an inorganic CaCO3 crystallite enveloped by an organic matrix. During growth, the individual crystallites fuse in an organized pattern. Growth begins right after seeding and continues until about a week after birth. During or shortly after growth, tens of thousands of otolith are anchored to the otoconial membrane atop the hair bundles, and some are in contact with the hair bundles. Cross‐section of the canine middle ear cavity showing its relationships to the external ear and inner ear. The three mammalian middle ear ossicles are formed by a process of endochondral ossification from neural crest of the first and second branchial arches: The first branchial arch gives rise to the malleus, incus, and anterior malleal ligament (Meckel’s cartilage). The second branchial arch (Reichert’s cartilage) gives rise to the manubrium of the malleus, long process of the incus, and the stapes. The outer parts of the stapedial footplate are of mesodermal origin The ossicles remain enveloped in mesenchyme until later in development, when the surrounding tissue involutes and they become suspended. The tympanic cavity extends along the middle ear space and connects the ossicles in a mesentery-like fashion to the wall of the cavity. The supporting ligaments of the ossicles develop within these mesenteries. Neural crest mesenchymal cells transform into epithelial cells that fuse with endoderm to repair the lining of the middle ear cavity. The middle ear then fills with air through the auditory tube, its connection with the pharynx. Because the malleus develops from the first branchial arch, its associated muscle, the tensor tympani, is innervated by the mandibular branch of the trigeminal nerve. Similarly, the stapedius muscle is innervated by the nerve to the second arch, the facial nerve. The mammalian malleus and incus are homologous to the articular and quadrate of the chick. The mammalian stapes is homologous to the single columella of birds. The auditory meatus of the external ear develops from the first pharyngeal cleft. Ectodermal cells at the blind end of the first pharyngeal cleft proliferate, forming a solid epithelial mass, the meatal plug. The plug, which persists for most of the foetal period, undergoes lysis in the perinatal period. The ectoderm of the expanded auditory meatus becomes apposed to the endodermal wall of the tympanic cavity separated only by a thin layer of mesenchyme (NC). Collectively, these three layers form the tympanic membrane: (1) an outer ectodermal lining at the bottom of the auditory meatus, (2) an inner endodermal lining of the tympanic cavity, (3) an intermediate layer of ectomesenchyme The cartilage of the external ear which surrounds the entrance of the external auditory meatus is derived from pharyngeal arches mesenchyme. Lateral view of the head of the embryo showing the six auricular Hillocks of His surrounding the dorsal end of the first branchial cleft (species specific). The hillocks enlarge asymmetrically in a species- specific manner, fuse and progressively develop into the adult auricle. The position of the auricle shifts from the base of the neck to its definitive location as gestation advances.  The ear, which functions as the organ of hearing and balance, has three subdivisions: an external ear (pinna), a middle ear within the tympanic cavity and an inner ear, which is encased in the temporal bone. Pharyngeal cleft ectoderm gives rise to the external ear meatus. Endoderm, from the first pharyngeal pouch, develops into the tympanic cavity and auditory tube. Otic placodes, composed of surface ectoderm, form the cochlea, vestibule and semicircular canals. They also give rise to the neuroblasts that will form the vestibulocochlear ganglion and sensory neurons. Periotic mesoderm surrounding the membranous labyrinth forms a cartilaginous shell that regresses proximally to form the perilymphatic duct. Neural crest derived mesoderm gives rise to the middle ear ossicles and parts of the tympanic cavity. Pharyngeal mesoderm gives rise to the outer ear auricle. The tympanic membrane is formed from layers of ectoderm, NC mesoderm and endoderm. Thank you!