Development of eye and ear

B.Sc. 2012

Embryonic development
Week 3: Beginning development of the brain, heart, blood cells, circulatory system, spinal cord, and digestive system. Week 4: Beginning development of bones, facial structures, and limbs (presence of arm and leg buds); continuing development of the heart (which begins to beat), brain, and nervous tissue. Week 5: Beginning development of eyes, nose, kidneys, lungs; continuing development of the heart (formation of valves), brain, nervous tissue, and digestive tract.

Week 6: Beginning development of hands, feet, and digits; continuing development of brain, heart, and circulation system. Week 7: Beginning development of hair follicles, nipples, eyelids, and sex organs (testes or ovaries); first formation of urine in the kidneys and first evidence of brain waves. Week 8: Facial features more distinct, internal organs well developed, the brain can signal for muscles to move, heart development ends, external sex organs begin to form. By the end of the embryonic stage, all essential external and internal structures have been formed. The embryo is now referred to as a fetus

Development of eye
The eyes of all vertebrates develop in a pattern which produces an "inverted" retina, in which the initial detection of light rays takes place at the outermost portion. The eye is derived from the neural tube (neuroectoderm), from which arise the retina proper and its associated pigment cell layer; the mesoderm of the head region, which produce the corneoscleral and uveal tunics; and the surface ectoderm, from which comes the lens.

Eye development
Earliest stage of eye development is the formation of the paired optic vesicles on either side of the forebrain. These growing diverticula expand laterally into the mesoderm of the head and develop a stalk-like connection to the main portion of the rudimentary central nervous system. In humans, this process begins at about 22 days of development; as the vesicles continue to grow, their connection to the brain becomes progressively narrower and more stalk-like. The forming stalks will eventually become the rudiments of the optic nerves.

Eye development
As this is occurring, the surface ectoderm thickens to form a lens placode, a region visible on the surface of the embryo. This transformation is triggered by the proximity of the optic vesicle, in a typical example of induction. Once the formation of the lens placode has begun, the expanding optic vesicle begins to invaginate to form a cup-shaped structure, and also to fold along its centerline, enclosing a small amount of angiogenic mesenchyme as it does so. This mesenchyme forms the hyaloid artery and vein, which supply the forming lens; and later, in the fully formed stage will become the central artery and vein of the retina.

Eye development
As the cup invaginates and folds, it is forming two distinct layers. The inner layer of the optic cup will eventually form the retinal tunic, including its light-sensitive elements. The outer layer of the optic cup will form the pigment epithelium layer, which lies outside the sensitive portion. The uveal and corneoscleral tunics eventually will differentiate from the surrounding mesoderm. Meanwhile, the surface ectoderm of the lens placode has thickened and is beginning to differentiate two distinct areas.

As the optic cup from the lateral wall of the forebrain comes close to the overlying non-neural ectoderm, the terminal induction of the lens placode takes place. The lens placode invaginates to form the lens vesicle. Fiber cells form and the crystalline gene family is activated.

Eye development
SUMMARY OF MAIN EVENTS The optic vesicles extend from the Diencephalon Optic vesicles come into close proximity to epithelial ectoderm Optic vesicle thickens & folds as optic cup Lens placode forms from epithelial ectoderm Lens placode infolds as future lens

TIME LINE
22 Days--Optic Groove Appears 24 Days--Optic Vesicle 26 Days --Optic Cup & Lens Placode 28 Days--Further folding OC & LP 33 Days--Sensory & Pigmented Retina 33 & 36 Days--Lens distinct

Eye development
The process of forming the eye by inversion of the optic vesicle and formation of the optic cup is common to all of the vertebrates. It produces an eye that has an inverted retina. The light-sensitive elements are located at the outer regions, and the neural connection to the brain must consequently come from the inner region, perforating through the rest of the layers in its course. The enclosure of the hyaloid artery and vein in the stalk provides for blood supply to the retina. The formation of the sclera, the cornea and the uveal tunic also have implications for the nature of the fully-formed eye. Since mesoderm is the only embryonic tissue with angiogenic potential, i.e., the capacity to form blood vessels, its participation in the formation of the uveal tunic and the sclera is necessary. The cornea, although it fuses with the sclera, is derived solely from ectoderm, and it is therefore avascular in its final form. This has clinical significance because it isolates the cornea from the immune system, creating a "privileged site" suitable for transplantation.. Formation of lens The first is the lens vesicle, and invagination of the surface placode that will separate and form the lens proper. As the lens rudiment detaches and drops into position, a space forms external to it that will become the anterior chamber of the mature eye. The surface ectoderm and the mesoderm beneath it differentiate into the cornea and the eyelids.

Induction in eye development

Chordamesoderm Induces Neural Tube Optic Cup Induces Lens Lens with or without the Optic Cup Induces Cornea Other combinations induce other components Eyes form at proper Place & Time Eye components appear in proper position & orientation

Lens Differentiation
Lens needs to clarify to allow light to pass Lens needs to be proper shape to focus light Cells at posterior side elongate Cells need to multiply to fill in this space Cells fill with clear crystallin proteins so light can pass through as well as be focused by the lens Germinative Region: Cells are actively dividing Region of Cell Elongation: Cells are beginning to change shape & Differentiate Cells differentiate into Fibre Cells Fibre Cells Densely Packed in Centre as Lens Nucleus

Pattern Generation

migration of retinal ganglion axons

Studied in non-mammalian vertebrates does apply to mammals neurons synapse in optic tectum of midbrain position of ganglion cells in inner margin of retina determined by cadherins on cell membranes growth of axon is directed both by presence of laminin and N-CAM on migratory surface netrin-1 made by cells at optic disc also aid migration (cells form optic nerve at disc) axons growing on glial cells toward optic tectum oriented by N-CAM, cadherins and integrins when reaching optic chiasma decision to go straight or cross brain governed by ephrin proteins and L1 and laminin adhesion molecules each axon goes to a specific site in tectum

Pattern Generation
Axons distinguish between different regions of optic tectum BY gradient of transcription factors which specify cells along a dorsal ventral axis dorsal retinal cells have high levels of TF Tbx5 while ventral cells have high levels of Pax2 TF induced by paracrine factors BMP4 and retinoic acid from nearby tissues in tectum gradient of ephrin proteins exists highest in posterior tectum ephrin protein repulse axons from temporal retina but not nasal retina activity dependent synapse formation also important here

Neural crest formation

Pax3 in Neural crest and Dermatomyotome

Muscle & dermis

expression of MITF depends on PAX3

Tissue-specific transcription factors act in a hierarchical and combinatorial network to specify different cell fates.

Embryonic induction and PAX6 expression

link between experimental embryology and genetics

DNA binding domains changes in gene expression

Signal from optic cup induces placode to develop Pax6 initiates and orchestrates program of eye development in optic cup and lens placode Human heterozygous-aniridia homozygotes-complete absence of eye Eyeless gene in Drosophila

DEVELOPMENT OF EAR

Ear development
Externally the pharyngeal arches are initially the most obvious external feature. Sensory placodes are present on the surface (but not obvious). Otic placode lies in the mesenchyme in the neck region The middle ear ossicles (bones) are derived from 1st and 2nd arch mesenchyme. The space in which these bones sit is derived from the 1st pharyngeal pouch

Origin of Three Ear Parts

inner ear
otic placode then otocyst

middle ear
1st pharyngeal pouch 1st and 2nd arch mesenchyme

outer ear
1st pharyngeal cleft 6 surface hillocks

Origin of inner Ear

Otocyst pair of surface sensory placodes (otic placodes) in the head region placodes fold inwards forming a depression pinches off entirely from the surface fluid-filled sac or vesicle (otic vesicle, otocyst) vesicle sinks into the head mesenchyme Inner Ear Development vesicle then extends and folds membranous labrynth
cochlea utricle and saccule endolymphatic duct semicircular canals

Then
innervated by CN VIII embedded in developing temporal bone

Middle Ear development ossicles (bones) arch 1 - malleus, incus arch 2 - stapes muscles (mesoderm) arch 1 - tensor tympani arch 2 - stapedius tympanic cavity first pharyngeal pouch extends as tubotympanic recess

Outer Ear development

surface hillocks (auricular hillocks)
three on pharyngeal arch 1 three on pharyngeal arch 2

external auditory meatus (canal)

1st pharyngeal cleft (groove)

Development Timing
Week 3 - otic placode, otic vesicle Week 5 - cochlear part of otic vesicle elongates (humans 2.5 turns) Week 9 - Mesenchyme surrounding membranous labrynth (otic capsule) chondrifies Week 12-16 - Capsule adjacent to membranous labrynth undegoes vacuolization to form a cavity (perilymphatic space) around membranous labrynth and fills with perilymph