Neuroscience LC3 Neuroembryology PDF

ll COURSE OUTLINE II. FIRST 3 WEEKS OF DEVELOPMENT I. Development of the Nervous System A. GESTATION II. First 3 weeks of Development Gestational Ag...

ll COURSE OUTLINE II. FIRST 3 WEEKS OF DEVELOPMENT I. Development of the Nervous System A. GESTATION II. First 3 weeks of Development Gestational Age A.Gestation ○ commonly used in clinical practice, beginning B.The Embryonic Period with the first day of the last menstrual C.Blastulation period. D.Gastrulation ○ the number of menstrual or gestational E.Neurulation weeks exceeds the number of post III. Development of the Central Nervous System fertilization weeks by 2. A.Formation of Primary and Secondary ○ Gestational age = Last Menstrual Period - Vesicles Time of the Consult B.Neural Development ○ Other Method: Ultrasound for confirmation C.Six Cellular Processes B. THE EMBRYONIC PERIOD IV. Stages of Neuronal Development 1. Sperm meets the egg A.Development of the Myelencephalon (Medulla Oblongata) Sperm enters the zona pellucida of the egg B.Development of the Metencephalon 2. Formation of the zygote (Pons and Cerebellum) When the sperm enters the plasma C.Development of the Mesencephalon membrane inside the zona pellucida, it will (Midbrain) merge with the genetic material of the egg. D.Development of the Prosencephalon ○ Cleavage: splitting of the cell into two (Forebrain) without growth. 1. Diencephalon 3. Development of Morula 2. Telencephalon Cluster of cells formed through cell division. V. Development of the Spinal Cord The cell splits into two, into four, then from A.Spinal Cord Embryonic Development four into eight, all while staying in the zona B.Three Distinct Layers pellucida. VI. Development of the Peripheral Nervous Appears like a blueberry System Compaction: different cells within the VII. Congenital Anomalies morula start to get closer and closer together. Differentiation: cells start being a little I. DEVELOPMENT OF THE NERVOUS different from each other. SYSTEM Mechanisms by which the CNS develops, and major developmental disorders arise. Figure 2. The Embryonic Period C. BLASTULATION Formation of blastocyst. Cells clump into the other side of the cell (forming the inner cell mass), leaving a cavity (blastocoel). During this time, the zona pellucida starts to Figure 1. Critical Periods of Prenatal Development disintegrate. Third week age of gestation: the heart and brain are The blastocyst would form a layer of already there. The last organ to mature and embryoblast and trophoblast maximize its potential is the brain. Bilaminar disk- the inner cell mass forms two layers of cells. The external layer is —------------------------------------------------------------------ called the epiblast and the internal layer is called the hypoblast. Primitive streak- formed on the surface of the bilaminar disk. It is a site where the epiblast layer starts to migrate down the bilaminar disk then go out of the hypoblast layer, forming the third layer (Trilaminar disk). BATCH 2028 1F 1 NEUROSCIENCE LC 3 SECONDARY NEURULATION PROCESS - Most caudal portion of the neural tube (sacral and coccygeal level of the cord) PROCESS OF NEURULATION Figure 3. Blastulation and Formation of Germ Layers D. GASTRULATION The formation of the three germ layers from the trilaminar disk: the ectoderm, mesoderm, and endoderm Figure 5. Neural Plate From the bilaminar embryo, a primitive streak would form above the ectoderm, causing invagination from the ectoderm going to the Formation of a thickened area of cells called the middle, forming the mesoderm and then the NEURAL PLATE which forms at the cranial end endoderm. of the embryo and grows at a cranial to caudal direction ↓ Figure 3. Germ Layers The nervous system comes from the ectoderm Figure 6. Cranial and Caudal end of the neural plate of the epiblast of embryoblast The cranial end represents the future region of The nervous system and epidermis originate the brain, while the caudal region represents the from the ectoderm. spinal cord. E. NEURULATION ↓ Figure 4. Neurulation Neural elements are formed here Beginning of the formation of the central nervous system and is the process whereby the neural plate forms into a neural tube Further differentiation of mesoderm cells into a chord structure Figure 7. Neural folds and Neural Groove ○ Notochord – Forms part of the vertebral disk and rarely will cause a tumor called At the end of the third week of development, the chordoma; The main purpose is that it will lateral edges of the neural plate become elevated induce a change in the ectoderm above it for and move together to form the NEURAL FOLDS; neurulation to occur the resulting space created by the folding of the PRIMARY NEURULATION PROCESS - Neural neural plate is called the NEURAL GROOVE. tube is formed from the neural plate (brain and spinal cord lumbar level). ↓ BATCH 2028 1F 2 NEUROSCIENCE LC 3 Mother is sick on the 26th-28th day of gestation during the closure of the caudal end, the child may have TETHERED CORD SYNDROME or LUMBAR MENINGOCELE. Hence, it is important for the mother to be healthy during pregnancy. III. DEVELOPMENT OF THE CENTRAL Figure 8. Neural Tube NERVOUS SYSTEM A. FORMATION OF PRIMARY AND The neural folds fuse together and the neural SECONDARY VESICLES plate transforms into the NEURAL TUBE, the precursor to the CNS. ↓ Figure 9. Cranial and Caudal end of neural tube Fusion of the neural tube usually begins in the Figure 11. Primary and Secondary Vesicles with adult deviation middle of the embryo extending to both cranial and caudal directions. The cranial part of the neural tube will form the ↓ ventricles: 3 PRIMARY VENTRICLES- Formed at week 4 of development ○ Prosencephalon (Forebrain) ○ Mesencephalon (Midbrain) ○ Rhombencephalon (Hindbrain) 5 SECONDARY VENTRICLES- Formed at week 5 of development ○ PROSENCEPHALON divides into: Telencephalon Figure 10. Formation of Neural Crest Diencephalon During the closure of the neural tube, cells on the ○ MESENCEPHALON remains crest of the neural folds detach, forming a new ○ RHOMBENCEPHALON divides into: cell population called the NEURAL CREST; Metencephalon these cells contribute to the formation of the Myelencephalon PNS. The caudal part of the neural cavity is the spinal Once the neural tube has completely fused, the cord. process of neurulation is complete. ADULT DERIVATIVES- Formed at week 6 ANTERIOR NEUROPORE closes on day 25, of development which is the 18-20 somite age TABLE 1. The primary divisions of the developing brain ○ Other references: CLOSURE AT Primary Primary Subdivision Adult CRANIAL END is 22-25 days of Vesicle Division Structures development POSTERIOR NEUROPORE closes on day 28, Telencephalon Cerebral hemisphere which is the 25 somite age Basal ganglia ○ Other references: CLOSURE AT Hippocampus CAUDAL END is 26-28 or 29 days of Forebrain Prosencep development Diencephalon Thalamus vesicle halon Hypothalamus (Forebrain) Pineal body Infundibulum CLINICAL CORRELATION: Midbrain Mesencep Mesencephalo Tectum Mother is sick on the 23rd day of the fetus’ vesicle halon n (Midbrain) Tegmentum development = disruption with the closure of the (Midbrain) Crus cerebri cranial portion which can result in different Hindbrain Rhombenc Metencephalon Pons problems such as OCCIPITAL MENINGOCELE vesicle ephalon Cerebellum and HYDRANENCEPHALY. (Hindbrain) Myelencephalon Medulla BATCH 2028 1F 3 NEUROSCIENCE LC 3 oblongata Neurons of the basal plates form the motor nuclei of: ○ CNs V, VI, VII Neurons of the ventro-medial part of each alar plate form these: ○ Main sensory nucleus of CN V ○ Sensory nucleus of CN VII ○ Vestibular and cochlear nuclei of CN VIII ○ Pontine nuclei Their axons grow transversely to enter the developing cerebellum, forming the transverse pontine fibers and the middle cerebellar peduncle. CEREBELLUM Figure 12. Formation of primary vesicles, secondary vesicles, and adult derivatives from the neural tube Rhombic lip develops into cerebellum Alar plate develops into four sensory tracts: B. NEURAL DEVELOPMENT ○ Pontine nuclei (cerebellar input) ○ Somatic afferent (general sensation from face, tongue, and extraocular muscles, CN V, VI, VII) ○ Special visceral afferent (taste, CN VII) ○ General visceral afferent (autonomic input from soft palate & pharynx, CN VII) Basal late develops into three motor tracts: ○ General visceral efferent (autonomic output to salivary and lacrimal glands, CN VII) ○ Special visceral efferent (innervation of muscles of face, via CN VII, and f mastication, Figure 13. Neural development from neuroepithelium via CN V) ○ Somatic efferent (innervation of lateral rectus muscles of eye, via CN VI) C. SIX CELLULAR PROCESSES Neurogenesis Cell migration Cell differentiation Synaptogenesis Neuronal cell death (apoptosis) Synaptic arrangement IV. STAGES OF NEURONAL DEVELOPMENT A. DEVELOPMENT OF THE MYELENCEPHALON (MEDULLA OBLONGATA) Figure 14. Cross section through the developing Basal plates - anterior thickenings of the neural metencephalon. Motor tracts are shown in green; sensory tracts are shown in orange. tube Alar plates - posterior thickenings of the neural tube C. DEVELOPMENT OF THE MESENCEPHALON Sulcus limitans - separates the two plates (MIDBRAIN) Neurons of the basal plates form the motor nuclei of: ○ CNs IX, X, XI, XII CEREBRAL AQUEDUCT OR AQUEDUCT OF Neurons of the alar plate form the sensory nuclei SYLVIUS - the cavity formed from the midbrain of: vesicle ○ CNs V, VIII, IX, and XII The neuroblasts in the basal plates will ○ Gracile and cuneate nuclei differentiate into the neurons forming the nuclei Other cells of the alar plate migrate ventrolaterally of: and form the olivary nuclei. ○ CNs III and IV ○ Red nuclei B. DEVELOPMENT OF THE METENCEPHALON ○ Substantia nigra (PONS AND CEREBELLUM) ○ Reticular formation Basis pedunculi - formed from the PONS enlargement of the marginal zone of each Arises from the ventral part of the basal plate metencephalon Tectum - formed from the two alar plates and Receives a cellular contribution from the alar the original roof plate part of the myelencephalon Sensory neurons of the superior and BATCH 2028 1F 4 NEUROSCIENCE LC 3 inferior colliculi - differentiated from the neuroblasts in the alar plates Four swellings representing the four colliculi appear on the posterior surface of the midbrain ○ Superior colliculi - associated with visual reflexes ○ Inferior colliculi - associated with auditory reflexes CN IV fibers emerge on the posterior surface of the midbrain CN III fibers emerge on the anterior surface. D. DEVELOPMENT OF THE PROSENCEPHALON (FOREBRAIN) Figure 15. Developing forebrain (transverse section) Optic vesicle - appears on each side of the forebrain at an early stage. ○ Along with the stalk, they form the retina and optic nerve The telencephalon develops a lateral diverticulum and its cavity, the lateral ventricle. Lamina terminalis - represents the rostral end of the neural tube The opening into each lateral ventricle is the future interventricular foramen 1. DIENCEPHALON Forms the greater part of the third ventricle The roof has a small diverticulum immediately anterior to the midbrain, forming the pineal gland Figure 16. Anatomy of the brain in 9-week ○ Associated with the sleep-wake cycle; it secretes melatonin. Choroid plexus of the third ventricle - formed from the remaining roof. Epithalamus - Masticatory and swallowing functions. Thalamus - Major relay of sensory input to cerebral cortex ○ Arises as thickening of the alar plate Hypothalamus - Master regulatory center (autonomic and endocrine) and also limbic system (emotion and behavior) Hypophysis/infundibulum - Posterior pituitary Figure 17. Telencephalon gland, secretes ADH and oxytocin. ○ Develops as a diverticulum from the floor of the diencephalon V. DEVELOPMENT OF SPINAL CORD ○ Originates the stalk and pars nervosa of the hypophysis Optic cup - Retina of eye A. SPINAL CORD EMBRYONIC 2. TELENCEPHALON DEVELOPMENT Forms the anterior end of the third ventricle The diverticulum on either side forms the cerebral hemisphere. BATCH 2028 1F 5 NEUROSCIENCE LC 3 - Remember: In the neural tube, the cranial part is The mantle layer will divide into two: the basal plate the brain, and the caudal part is the spinal cord. and alar (dorsal) plate. The dorsal (alar) will be - 6 weeks 2 clusters of neuroblasts sensory and the ventral (basal) will be motor. The Alar plate - becomes interneurons, axons form motor basal plate and sensory alar plate are the white matter. Neuroblast in the alar plate separated on each side by the sulcus limitans. will become the sensory cells of the posterior column. Basal plate - becomes motor neurons, axons will grow to effectors. Neuroblasts from in the basal plate will form the motor cells of the anterior column (horn). - Neural crests from the dorsal root ganglia sensory neurons, axons grow into the dorsal aspect of the cord. B. THREE DISTINCT LAYERS Ependymal zone/Ventricular zone ○ Lined with columnar epithelial cells. Mantle zone/Intermediate Zone ○ Where the neurons are located. ○ Consists of cell bodies and dendrites. ○ The intermediate zone will form the gray matter of the spinal cord. Marginal zone ○ Consists of axons ○ The nerve fibers in the marginal zone become myelinated and form the white matter of the spinal cord. The lateral column is only present from T1 to L2 which is an important part of the autonomic nervous system. In the cerebral cortex, neurons are located in the periphery and the white matter or axons are in the middle part. In contrast, in the spinal cord, the neurons are in the midline while the white matter or axons are on the outside. Remember: Sensory is afferent and motor is efferent. There are a lot of descending and ascending tracts in the spinal cord which all have lamination. E.g. Lateral spinothalamic tract BATCH 2028 1F 6 NEUROSCIENCE LC 3 VI. DEVELOPMENT OF THE PERIPHERAL NERVOUS SYSTEM Embryonic Development Ontology Tree Enteric Ganglia - neural crest cells migrate to the gut. Contains cell bodies that are part of the enteric nervous system. 3. Formation of Motoneurons in Ganglia Not derived from neural crest cells but from the neural tube. Extend their axons to innervate muscles and glands. 4. Migration of All Associated Glia Migrate to the ganglia and differentiate into their mature form. Developing Peripheral Nervous System 1. Migration of Neural Crest Cells PNS originates from neural crest cells. migrate to various parts of the embryo and differentiate into a variety of cell types, neurons and glial cells of the PNS. 2. Formation of Ganglia Dorsal Root Ganglia - neural crest cells migrate dorsolaterally. Contains the cell bodies of sensory neurons. Parasympathetic and Sympathetic Ganglia - neural crest cells migrate ventrally located near or within the organs they innervate. Contains cell bodies that are part of the autonomic Neural Crest Migration nervous system. BATCH 2028 1F 7 NEUROSCIENCE LC 3 VI. CONGENITAL ANOMALIES 1. Dorsal Induction a. Chiari malformations b. Encephaloceles 2. Ventral Induction a. Holoprosencephaly b. Septo Optic dysplasia c. Dandy-Walker malformation 3. Neuronal Proliferation and Histogenesis a. Neurofibromatosis b. Tuberous sclerosis c. Primary hydranencephaly 4. Migration a. Schizencephaly b. Argyria and pachygyria c. Gray matter heterotopias d. Dysgenesis of corpus callosum Occipital encephalocele - This parasagittal MR image reveals brain parenchyma that has herniated through a posterior calvarial defect. Although the protrusion contains a large vessel, represented by a linear signal void. It is difficult to identify possible ventricular structures because of distortion. Meningocele - covered with full-thickness skin. The meninges project through the defect In the vertebral arches, forming a cystic swelling beneath the skin Chiari II malformation - T1 weighted MR image. and containing CSF, which communicates with the Note the towering cerebellum above the dysplastic subarachnoid space. tentorium (arrows). There are also distortions of the cerebellar folla and hydrocephalus. BATCH 2028 1F 8 NEUROSCIENCE LC 3 Schizencephaly - Axial T1-weighted brain MRI showing open-lip schizencephaly with absent septum and reduced right temporal lobe. References: BATCH 2028 1F 9