SEM_16_Central Nervous System. Eye and Ear_0dc0d0fdd91f99b4d1327cf10f075acc.docx

A quote The human brain has 100 billion neurons, each neuron connected to 10 thousand other neurons. Sitting on your shoulders is the most complicated object in the known universe. Michio Kaku Learning objectives Consider briefly the origin of the neural tube and neural crests. Describe how neuro...

A quote The human brain has 100 billion neurons, each neuron connected to 10 thousand other neurons. Sitting on your shoulders is the most complicated object in the known universe. Michio Kaku Learning objectives Consider briefly the origin of the neural tube and neural crests. Describe how neurons and glial cells differentiate. Understand the development of the spinal cord. Understand the formation of the brain’s components. Understand the development of organs related to the special senses of vision, hearing and balance. Neural tube and neural crests formation Although the formation of the neural tube and neural crests have already been considered in a previous chapter, it can be appropriate to introduce this chapter recapitulating the major events in this development: Neural plate. It is a longitudinal thickening in the dorsal midline of the embryo formed when the ectodermal cells overlaying the notochord become a tall columnar epithelium, in contrast with the thinner surrounding ectoderm that produces the epidermis of the skin. Neural Groove. It is formed when the neural plate deepens in the middle. Neural tube. Ultimately, the dorsal edges of the neural groove meet and coalesce in the midline to form a closed tube composed of columnar neuroepithelial cells surrounding a central neural cavity. Neural crests. At the same time that the neural tube moves downwardly separating from overlaying ectoderm, some cells become detached from the tube and collect bilaterally to it to form the neural crests. https://sway.office.com/3t5TVYZ4MaOCjARq#content=Yeut3QQCsrfOxm - Early development of the Neural Tube The neural tube is the origin of the central nervous system (CNS), which consists of the brain and spinal cord. The cavity of the neural tube becomes the cavities of the central nervous system: the ventricles of the brain and central canal of the spinal cord. Some cells of the neural crest differentiate into neurons of the peripheral nervous system (PNS); these cells give rise to the ganglia, nerve cell clusters or groups of nerve cell bodies located in the autonomic nervous system and sensory system. In addition, other cells migrate to a variety of location to give rise to a range of cell types. For instance, they become the myelin-forming cells (Schwann cells) of the PNS; the catecholamine forming cells (chromaffin cells) located in the medulla of the adrenal gland; the melanin forming cells (melanocytes) of the skin. Also, in the cranial region, cells from the neural crest migrate into the pharyngeal arches to form the branchial ectomesenchyme which is the origin of a substantial number of the musculoskeletal structures of the head. https://sway.office.com/3t5TVYZ4MaOCjARq#content=6LPeMjRSu8It6j - Early development of the Neural Crests. Formation of the neurons and glial cells The neuroepithelial cells located in the wall of the neural tube are the stem cells for the formation of the neurons and most of the glial cells (astrocytes and oligodendrocytes). Microglial cells are considered of mesodermal origin because they derive from cells associated with invading blood vessels. Once the neuroblast and glial cells populations have been formed, the remaining neuroepithelium forms the lining epithelium of the central cavities of the CNS (the ependymal canal in the spinal cord and the ventricles in the brain). The process of cellular differentiation in the central nervous system can be summarised as follow: The neural tube is initially lined with a pseudostratified columnar epithelium which neuroepithelial cells have processes that contact the inner and outer surfaces of the neural tube. During development, the neuroepithelial cells undergo continual mitotic division in a peculiar manner: During interphase (DNA synthesis), the nucleus and perikaryon move away from the neural cavity. For mitosis division, the nucleus moves toward the neural cavity and the cell becomes spherical and loses its connection to the outer surface of the neural tube. This inward-outward nuclear movement is repeated at each cell division. Some cell divisions are different because the daughter cells become either the progenitor cells for the neurons, neuroblasts or the precursors for glial cells, glioblasts. Neuroblasts and glioblasts detach from the neuroepithelium and migrate away from the lumen toward an adjacent region. The zone where the bodies of the migrated neuroblasts and glioblast are gathered is called the mantle layer. This layer surrounds the central neuroepithelium and will form the grey matter of the nervous system. The outermost layer of the neural tube, the marginal layer, contains the long processes, called nerve fibres, produced from the neuroblasts located in the mantle layer. This layer will be transformed in the white matter of the nervous system, for the whitish colour of the myelin that quickly surrounds most of the newly-formed nerve fibres. After development, the cells that do not leave the neuroepithelium remain in the centre of the nervous system forming the ependymal layer/ventricular layer which forms the lining of the neural cavity (the ependymus/ventricle). https://sway.office.com/3t5TVYZ4MaOCjARq#content=YG3UsgQCFl3blI - Cytodifferentation of the celllular components of the central nervous system Sculpting neuronal circuits Sculpting means removing excess material to achieve the desired effect. To ensure that all targets get sufficient innervation, initial neural development produces an excessive number of neurons along with a profuse, random growth of neuronal processes. Neurons that fail to contact an appropriate target will degenerate and disappear, because they do not receive sufficient neurotrophic molecules (selective pruning). Selective degeneration of neurons and neuronal processes is the result of functional competition. More appropriate targets are associated with more neurotransmitter release, which reinforces more neural activity. Thus, developmental remodelling is a consequence of electrochemical activity related to experiences and behaviour. Neuromuscular innervation illustrated this process. Initially, each motoneuron innervates an excessive number of muscle fibres and each muscle fibre is innervated by a large number of motoneurons. Ultimately, each muscle fibre will retain only a single synapse-associated with one single motoneuron, while those motoneurons that fail to retain any connection eventually disappear. The survivor neurons (winners) are those having fewer branches that can release more neurotransmitter per terminal branch, giving them a competitive advantage over neurons with many more processes. Nervous system remodelling is also driven by experiences that promote selective growth and pruning of neuronal synapses throughout life. For instance, in the human prefrontal cortex, synaptic density peaks during the first year of age and then decline to half that synaptic density in adults. Different timelines for neural degeneration through lie can be found in the literature. The data about neural regeneration are more controversial. As a rule, it is difficult to replace any neural loss once the development is finished. It is believed that all, or at least the great majority of neurons that make up the nervous system are produced during development. Mature neurons become such a specialised cell that they are incapable of undergoing cell division. However, some data seems to contradict the aforementioned generalisation. The best-known examples are the hippocampus and the olfactory bulb, where new neurons are formed in adults from neural stem cells or neuroblasts. Divisions of the neural tube Early in development, the cranial end of the neural tube forms three primary enlargements or vesicles that further divide into the five secondary components of the brain. Caudal to the brain the neural tube develops into the spinal cord. The developing brain also undergoes three flexures: the cervical flexure, at the junction between the brain and spinal cord; the midbrain flexure, at the level of the midbrain; the pontine flexure, in-between the other flexures. Apart from the cervical flexure that partially persists, the brain flexures generally straighten out and disappear over development in domestic animals. https://sway.office.com/3t5TVYZ4MaOCjARq#content=zbtG2aEtGOOOE0 - Brain vesicles Early organisation of the neural tube The continual addition of neuroblasts to the mantle layer results in the formation of two bilateral thickenings called the dorsal (alar) and ventral (basal) plates. These two parts are limited by a bilateral indentation, the sulcus limitans, that appears in each lateral wall of the neural cavity. This division is decisive in determining the functional role of the neurons associated with each plate. Cells within the alar plate develop into afferent neurons or sensory neurons that receive input from the peripheral nervous system. Cells within the basal plate develop into efferent neurons or motor neurons that send axons toward the peripheral nervous system. In the midline, the neural tube is closed by the dorsal roof plate and the ventral floor plate, which are related to the development of pathways for fibres crossing from one side of the neural tube to the other. Although the formation of the neural tube is one of the earliest events during embryo development, the differentiation of the specific structures and their functional integration is a complex process that extends over a long period of time. Among the domestic animals, carnivores are born with a nervous system that does not mature until about six weeks postnatally; consequently, mature behaviour is correspondingly delayed in these species. In contrast, herbivores are born with an almost mature nervous system. Main events in the development of the spinal cord The neural cavity becomes a small central canal lined by ependymal cells. The growth of the alar and basal plates, but not of the roof and floor plates, results in the formation of symmetrical columns of the grey matter referred to as the dorsal horn and ventral horn, derived from the alar plate and ventral plate, respectively. Once development is completed, the grey matter becomes shaped like a butterfly, with prominent dorsal and ventral grey horns arranged around the central canal. Besides the dorsal and ventral horns, in some region of the neural tube, the mantle layer forms an additional small projection of grey matter between the alar and basal plates. This is the lateral horn, which contains the neurons of the autonomic nervous system. The marginal layer becomes white matter, which is subdivided bilaterally into the dorsal funiculus (bundle), lateral funiculus, and ventral funiculus. Two enlargements of the spinal cord are found at the segments that innervate the limbs: cervical and lumbosacral enlargements. They are the result of the greater numbers of neurons in those segments, due to less neuronal degeneration compared to segments that do not innervate limbs. https://sway.office.com/3t5TVYZ4MaOCjARq#content=3ZdiksZxZjEuma - Development of the spinal cord Main events in the development of the Central Nervous System (CNS) Rhombencephalon (hindbrain) The rhombencephalon or hindbrain is the most caudal region of the brain. It is composed of the myelencephalon (medulla oblongata) and metencephalon (pons and cerebellum). https://sway.office.com/3t5TVYZ4MaOCjARq#content=LxE5U4sHapdaGa - Early rhombencephalon organisation Myelencephalon (medulla oblongata) The alar plates move laterally, and the cavity of the neural tube expands dorsally forming a rhomboid-shaped cavity called the fourth ventricle; the roof plate forms the roof of the fourth ventricle which is reduced to a layer of ependymal cells covered by the pia mater; a choroid plexus develops bilaterally in the roof of the ventricle to secrete the cerebrospinal fluid. The alar and basal plates, representing the motor and sensory area are located ventrally to the fourth ventricle on each side of the midline, with the alar plate located lateral to the basal plate. Unlike in the spinal cord, the white and grey matter derived from the marginal and mantle layers become intermixed. https://sway.office.com/3t5TVYZ4MaOCjARq#content=abPcDcYYY0CwT8 - Development of the myelencephalon Metencephalon (pons and cerebellum) The formation of the bilateral rhombic lips is the first evidence of cerebellar development; the lips are expansions of the alar plate into the roof plate; the rhombic lips merge medially, forming a midline portion, the vermis, and two bulging lateral masses, the cerebellar hemispheres. Cerebellar components develop to form a cerebellar plate which initially consists of a neuroepithelial, a mantle, and a marginal layer. Cells from the neuroepithelium migrate through the mantle layer to the marginal layer to form the external granular layer and the superficial cortical layer (cerebellar cortex). Simultaneously, some neuroepithelial cells, in a second wave, migrate into the marginal layer to form the Purkinje cells. Deep paraventricular cerebellar nuclei are formed by non-migrating neuroblasts in the mantle layer. https://sway.office.com/3t5TVYZ4MaOCjARq#content=6Nh3VaI1CgW4Z0 - Development of the metencephalon Mesencephalon (midbrain) The neural cavity of the midbrain becomes the mesencephalic aqueduct which is not a ventricle because it is surrounded by brain tissue and thus it lacks a choroid plexus. Alar plates form two pairs of dorsal bulges which become the rostral and caudal colliculi (associated with visual and auditory reflexes, respectively). The basal plate gives rise to the oculomotor (III) and trochlear (IV) nerves which innervate muscles that move the eyes. https://sway.office.com/3t5TVYZ4MaOCjARq#content=Ein0VYgfsgmlW8 - Development of the mesencephalon Prosencephalon (forebrain) The prosencephalon or forebrain is derived entirely from the alar plate. It comprises the diencephalon and the telencephalon. Diencephalon The neural cavity expands dorsoventrally and becomes the narrow third ventricle; choroid plexuses develop bilaterally in the roof of the third ventricle to secrete the cerebrospinal fluid. The floor of the third ventricle gives rise to the neurohypophysis (neural lobe of the pituitary gland). The mantle layer of the diencephalon gives rise to the thalamus, hypothalamus, and epithalamus; the thalamus enlarges to the point where right and left sides meet at the midline and obliterate the centre of the third ventricle. The optic nerve develops from an outgrowth of the wall of the diencephalon. Telencephalon (cerebrum) The telencephalon comprises two bilateral hollow outgrowths that become the right and left cerebral hemispheres. The cavity of each outgrowth forms a lateral ventricle that communicates with the third ventricle via an interventricular foramen (in the wall of each lateral ventricle, a choroid plexus develops that is continuous with a choroid plexus of the third ventricle via an interventricular foramen). The mantle layer surrounding the lateral ventricle in each hemisphere gives rise to basal nuclei and cerebral cortex. https://sway.office.com/3t5TVYZ4MaOCjARq#content=tCQBJGNx8nAnpA - Development of the prosencephalon Main events in the development of the Peripheral Nervous System (PNS) The peripheral nervous system comprises all the parts of the nervous system outside the brain and spinal cord. It consists of cranial and spinal nerves and their associated ganglia and supportive cells. One classification of the PNS groups the nerves into two main types: the somatic nervous system (innervating skin and skeletal muscles) and the autonomic or visceral nervous system (innervating vessels and viscera). Both somatic and visceral nerves can contain efferent (motor) nerve fibres that conduct impulses from the CNS and afferent (sensory) nerve fibres that conduct impulses toward the CNS. The embryonic origin of these nerve fibres can be summarised as follows: The somatic efferent fibres arise from motor neurons which are derived from the basal plate. In the spinal cord, the cell bodies of the motor neurons are located in the ventral horn and their somatic efferent fibres leave the spinal cord through the ventral root of the spinal nerves. The visceral efferent pathway involves two neurons: Preganglionic neurons, which arise from the basal plate of the neural tube and maintain their cell bodies within the CNS. Postganglionic neurons, which arise from neural crests and migrate to form the autonomic ganglia outside the CNS. The visceral and somatic afferent fibres arise from cells migrated from the neural crests which cell bodies become grouped in the sensory ganglia. In the spinal nerves, their cell bodies are gathered in the dorsal root ganglia and enter the spinal cord through the dorsal root; the afferent neurons for special senses also originate from ectodermic placodes. The glial cell of the PNS is the neurolemmocyte, also called the Schwann cell. They arise from neural crests and migrate throughout the PNS, ensheathing and myelinating axons and forming satellite cells in ganglia. Formation of the meninges The meninges are three membranes that surround the CNS and the roots of spinal and cranial nerves. The three meningeal layers (dura mater, arachnoid, and pia mater) are formed as follows. The mesenchyme surrounding the neural tube aggregates into two embryonic layers. The outer layer forms the dura mater. Cavities develop and coalesce within the inner layer, dividing it into the arachnoid and the pia mater. The cavity becomes the subarachnoid space which contains cerebrospinal fluid. Main events in the development of the eye Both eyes are derived from a single optic field in the cranial neural plate. The single field separates into bilateral fields associated with the diencephalon. The development of each eye comprises the following main events: The optic vesicle is formed as a lateral diverticulum from the diencephalon, to which it remains attached by an optic stalk. The optic stalk becomes the optic nerve as it fills with axons travelling from the retina to the brain. The developing optic vesicle and stalk have a groove on their inferior surfaces called the optic, or choroidal fissure, through which blood vessels gain access to the optic cup as well as the lens vesicle. The choroidal fissure will eventually fuse, completing the inferior eye wall and enclosing the vessels in a canal in the optic stalk. A lens placode develops in the surface ectoderm where it is contacted by the optic vesicle. The lens placode induces the optic vesicle to invaginate and to form an optic cup. Meanwhile, the lens placode invaginates to form a lens vesicle that invades the concavity of the optic cup. The optic cup forms the retina and contributes to the formation of the ciliary body and iris. The outer wall of the cup forms the outer pigmented layer of the retina, and the inner wall forms neural layers of the retina. The lens vesicle develops into the lens, consisting of a number of layers of fibres enclosed within an elastic capsule. The vitreous body forms in the centre of the optic cup posterior to the lens. It is comprised of a gel-like substance called vitreous humour derived from mesenchymal cells and from the neuroectoderm of the optic cup. A hyaloid canal runs in the centre of the vitreous body from the optic disc to the lens. In foetal life, it contains a prolongation of the central artery of the retina, the hyaloid artery, which supplies blood to the developing lens. When the lens matures later in foetal life, the distal end of the hyaloid artery will disintegrate, and its proximal end will persist as the central retinal artery. The ectomesenchyme from the neural crests that surrounds the optic cup condenses to form an inner and an outer layer, the future choroid and sclera, respectively. The ciliary body and iris are formed at the anterior rim of the optic cup. The inner non- pigmented layer and the outer pigmented layer of the iris are continuous with the neural and pigmentated layer of the retina. The stroma of the iris and the ciliary body develop from neural crest cells that migrate into the area. Within the stroma of the iris, the sphincter pupillae and dilator pupillae muscles develop from optic cup neuroectoderm. In contrast, the ciliary muscle, which is responsible for changing the shape of the lens, is derived from overlying mesenchyme. The colour of the eye is determined by the amount of melanin distributed in the outer pigmented layer of the iris and in the stroma of the iris. A pupillary membrane develops from the mesenchyme in the centre of the iris as a source of blood supply for the lens in the foetus. It normally atrophies before or shortly after birth. The anterior chamber (between the cornea and the iris) and the posterior chamber (between the iris and the lens) develop as clefts in the mesenchyme situated between the cornea and the lens. The eyelids are formed by upper and lower folds of ectoderm, each fold includes a mesenchyme core; the folds adhere to one another, but they ultimately separate either prenatally (ungulates) or approximately two weeks postnatally (carnivores); ectoderm lining the inner surfaces of the folds becomes the conjunctiva, and lacrimal glands develop by budding of the conjunctival ectoderm. Skeletal extraocular eye muscles that move the eye are derived from rostral somitomeres (innervated by cranial nerves III, IV, and VI). Clinical considerations: The ungulate retina is mature at birth, but the carnivore retina does not fully mature until about some weeks postnatally. Congenital retinal detachment occurs when the inner neural and outer pigmented layers of the retina, derived from the inner and outer layers of the optic cup, do not fuse but are only held in place by the pressure of the vitreous body. Coloboma describes conditions where normal tissue in or around the eye is missing at birth. In the developing eye, a gap, known as the choroidal fissure, appears at the bottom of the cup and stalks that eventually form the eye. This fissure generally closes, but if it does not a coloboma or space forms. 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 the pupil. https://sway.office.com/3t5TVYZ4MaOCjARq#content=EZcqzXoNu5BwfM - Development of the eye Main events in the development of the ear The ear has three components: the external ear, middle ear, and inner ear. The inner ear contains the sense organs for hearing (cochlea) and for detecting head acceleration (vestibular apparatus); the latter is important in balance. The middle ear contains bones (ossicles) that convey vibrations from the tympanic membrane (eardrum) to the inner ear. The outer ear channels sound waves to the tympanic membrane. Ear development can be summarised as follow: Inner ear An otic placode develops in surface ectoderm adjacent to the hindbrain; the placode invaginates to form a cup which then closes and separates from the ectoderm forming an auditory vesicle (otocyst). Some cells of the placode and vesicle become neuroblasts which give rise to the afferent neurons of the vestibulocochlear nerve (VIII). The otic vesicle undergoes differential growth to form the cochlear duct and the semi- circular ducts of the membranous labyrinth. The otic vesicle itself soon begins to elongate and differentiates into two distinct parts: the utricle dorsally, and the saccule ventrally. An otic capsule, composed of cartilage, surrounds the otocyst. The cartilaginous otic capsule undergoes similar differential growth to form the osseous labyrinth within the future petrous part of the temporal bone. Middle ear: The dorsal part of the first pharyngeal pouch forms the lining of the auditory tube and tympanic cavity (in the horse a dilation of the auditory tube develops into the guttural pouch). The malleus and incus develop as endochondral bones from ectomesenchyme in the first pharyngeal arch while the stapes develops similarly from the second arch (in fish, these three bones have different names; they are larger and function as jawbones). Outer ear: The tympanic membrane is formed by apposition of the endoderm and ectoderm where the first pharyngeal pouch apposes to the cleft between the first and second pharyngeal arches. This first pharyngeal groove develops into the external auditory canal while the adjacent first and second pharyngeal arches expand laterally to form the wall of the canal and the auricle (pinna) of the external ear. https://sway.office.com/3t5TVYZ4MaOCjARq#content=kWJFnN0grcnRRX - Development of ear