Embryologic Development of Central Nervous System PDF

(008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21...

(008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 OUTLINE C. Flexures of the Brain 1. Cephalic (Mesencephalic) Flexure I. Introduction 2. Pontine Flexure A. Embryology a. 4th ventricle 1.Prenatal Development 3. Cervical Flexure a. Embryonic Period V. Development of the Ventricular System b. Fetal Period A. Cavities of Brain Vesicles 2. Postnatal Development B. 4 Ventricles of the Brain B. Neuroembryology VI. Clinical Correlates 1. NS A. Hydrocephalus 2. Neural Ectoderm B. Dandy-Walker Syndrome a. Neural tube VII. Primary Brain Vesicles b. Neural Crest Cells A. Prosencephalon (Forebrain) c. Ectodermal Placodes 1. Diencephalon 3. Genesis of Nervous System and Special a. Hypothalamic Sulcus Sense Organs b. Neurohypophysis 4. Formation of the Neural Tube c. Epithalamus a. 6th day of Embryonic Life d. Pineal gland b. 20th day of Embryonic Life 2. Telencephalon 5. Formation of Neural Crest Cell a. Lamina Terminalis 6. Formation of Ectodermal Placode b. Lateral Diverticula a. Cell Population c. Corpus Striatum b. During Neurulation d. 3 Meninges/Membranes 7. Neural Crest Cells Differentiation B. Mesencephalon (Midbrain) II. Clinical Correlations 1. Crus Cerebri A. Anencephaly 2. Corpora Quadrigemina B. Rachischisis C. Rhombencephalon (Hindbrain) III. Development of the SC 1. Developing 4th ventricle A. Histogenesis of Neural Tube 2. Functional Columns of Gray Matter in the 1. 5th week of Embryonic Life Brainstem a. Neural Tube Zones 3. Roof of 4th ventricle, Tela Choroidea, Choroid 2. Current Theory Plexus, Rhombic Lips B. Development of Functional Columns 4. Pons 1. Columns of the Lamina VIII. Clinical Correlates a. 2 Afferent Column of Alar Lamina b. 2 Efferent Column of Basal Lamina C. Positional Changes of the SC I. INTRODUCTION 1. 8th week 2. 24th week Embryology 3. Birth 4. Adults Is based actually on neuroanatomy, it is neuroanatomy 5. Termination of SC in relation to Vertebral oriented and it is the first system to start and develop Canal at Various Stages of Development before the development of the embryo. IV. Development of the Brain Science that deals with the development & growth of an A. End of 4th week individual within the female organ the uterus from 1. Primary Brain Vesicles fertilization occur of an ovum to birth a. Prosencephalon (Forebrain) b. Mesencephalon (Midbrain) Benefits: c. Rhombencephalon (Hindbrain) a. Understand the rationale of the structure and function of B. 5TH week each body system 1. Differentiation of Prosencephalon to: b. Understand the factors causing many congenital a. Telencephalon anomalies pertaining to neuroembryology b. Diencephalon c. Mesencephalon Prenatal development d. Rhombencephalon - Period of development from fertilization to birth Page 1 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 - Before birth the individual is developing - Development of an individual continues even after - Begins with a single cell called zygote (fertilized birth up to 20’s or age of 25 years ovum) & culminates or end after 9 months (38 weeks or 266 days) with a more complex organism Neuroembryology call newborn (made up of billion cells ) Morphogenesis Nervous System -derived from the ectoderm except its - Process in prenatal development which includes: blood vessels & some neuroglial elements a. cell division Neural Ectoderm b. transformation or specialization - Specific cell population of early ectoderm c. migration - Gives rise to entire NS & special sense organs d. apoptosis/program cell death - Differentiates into three structures: - during this process, the genetic or environmental 1. Neural tube factors may affect the normal development of baby & - Gives rise to the CNS. The central nervous system cause congenital anomalies (CNS) appears at the beginning of the third week as a slipper shaped plate of thickened ectoderm, the neural plate, in the mid-dorsal region in front of Clinical Divisions of Prenatal period: the primitive node. Its lateral edges soon elevate to 1. Embryonic period form the neural folds. With further development, the - Extends from fertilization to the end of 8th week of neural folds continue to elevate, approach each IUL other in the midline, and finally fuse, forming the - Developing organism is called an embryo neural tube. 2. Fetal period - Extends from the beginning of 9th week (3rd month) 2. Neural crest cells until birth - Form the PNS and to several non-neural cell types, - Further sub-divided into two parts: including smooth muscle cells of the cardiovascular a. Pre-embryonic period system, pigment cells in the skin, and craniofacial b. Embryonic period proper bones, cartilage, and connective tissue. Embryological Divisions of Prenatal period: 1. Pre-embryonic period 3. Ectodermal placodes - Extends from conception (fertilization) to the end of - Contribute to CN sensory ganglia, hypophysis & 2nd week of intrauterine life (IUL) inner ear. These structures form at stereotypical - Morphogenic events: positions reflecting the importance of localised cues a. Fertilization in their development and subsequently undergo b. Transportation of zygote through the differential morphogenesis to generate key uterine tube components of the cranial sensory apparatus. The c. Mitotic divisions/cleavage ectodermal placodes comprise the d. Implantation adenohypophyseal, the olfactory, the lens, the e. Formation of primordial embryonic tissues ophthalmic and maxillomandibular trigeminal, the 2. Embryonic period otic, lateral line and the epibranchial placodes - Extends from beginning of the 3rd week to the end - of the 8th week of IUL - Morphogenic events : a. Differentiation of germ layers become into specific body organs b. Formation of placenta, umbilical cord & extraembryonic membranes 3. Fetal period - Extends from beginning of the 9th week to birth (+) tremendous growth & specialization of body structures those organs that are formed now tend to function accordingly Postnatal Development Page 2 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 Figure 2. Formation of the Neural tube & Genesis of the Nervous Figure 1. Prenatal Development System and Special Sense Organs 20th day of embryonic life Formation of the Neural Tube - Fusion of neural folds begins in the midline or 16th day of embryonic life middle part (4th somite region) - Ectoderm thickness in midline forming neural plate - Simultaneously proceeds in the cephalic & caudal - Somatic mesoderm develops on either side of the directions going to the head and tail region notochord - Fusion at the cranial & caudal ends of neural tube - Margins of neural plate are elevated as neural is somewhat delayed, forming small openings folds called anterior & posterior neuropores - Center of the plate sinks creating neural groove - Neural tube & overlying amniotic cavity remain - Neural folds gradually move together toward the temporarily in open communication with each other midline & fuse to form a cylindrical neural tube that through these pores loses its connection with the surface ectoderm - Some of the neural crest cells will migrate somewhere on the periphery of the neural tube - Process of neural tube formation is called Neurulation Figure 3. Dorsal aspect of a human embryo at day 19 (A) and day 20 (B). Note the rapid progression of somite formation, the appearance of the neural fold, and the deepening of the neural groove from day 19 to day 20 in development. Anterior Neuropore - Closes (middle of 4th week) at 18-20 somite stage or region. Closure of the cranial neuropore proceeds cranially from the initial closure site in the cervical region and from a site in the forebrain that forms later. This latter site proceeds cranially, to close the rostralmost region of the neural tube, and caudally to meet advancing closure from the cervical site - Posterior Neuropore - Closes (end of 4th week) at 25 somite stage - By the time the neural tube is completely closed, it is divided into an enlarged cranial part & an Page 3 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 enlarged cranial part & an elongated caudal part, During Neurulation which gives rise to the brain & spinal cord - Neural crest cells are detached then they will migrate underneath the ectoderm on the periphery of the newly formed neural tube - Neuroepithelial cells get incorporated into the surface ectoderm - Areas of neuroepithelium within the surface ectoderm are termed Ectodermal Placodes Figure 4. Changes in the morphology of the embryo in the embryonic period Formation of Neural Crest Cells - When neural folds come together & fuse, cells at the tips of neural folds break away from the neurectoderm to form the Neural Crest cells - Surface ectoderm of opposite side over the neural tube. - Neural crest cells originate in the ectoderm at the margins of the neural tube and, after a phase of epithelial-mesenchymal transition and extensive Figure 5. Neural Crest Cells Differentiation migration, settle down in different parts of the body - This illustration shows some neural crest cells will to contribute to the formation of a plethora of differentiate to become schwann cells, adrenal different tissues and organs. medulla, autonomic ganglia, dorsal root ganglia and cranial nerves Neural Crest cells differentiate to form: II. CLINICAL CORRELATION a. Cells of DRG b. Sensory ganglia of CN Anencephaly. c. Autonomic ganglia d. Adrenal medulla Anencephaly (craniorachischisis) e. Chromaffin tissue Failure of the cephalic part of the neural tube to close f. Melanocytes Due to defective development of the neural tube g. Schwann cells Associated defective development of the vault of the skull Formation of Ectodermal Placodes -Arise from common panplacodal ectoderm (PPE) a Characteristics features: horseshoe-shaped region of ectoderm surrounding the anterior neural plate and neural crest. Each a. Vault of the skull is absent placode then differentiates to eventually have b. Brain is represented by a mass of degenerated tissue different developmental fates. These sensory exposed to the surface placodes will later contribute key components of c. Cord is open in the cervical region each of our special senses (vision, hearing and d. Child appears with prominent eyes bulging forward , & smell). chin is continuous with chest due to absence of neck - Prior to the neural tube closure, the neural fold contains two types of cell populations: 1. Neural Crest cells 2. Neuroepithelial cells Page 4 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 Histogenesis of Neural Tube Neural tube increases in thickness due to repeated mitosis the division of the cells of its epithelial lining 5th week of embryonic life - Transverse section of recently closed neural tube - Neural Tube layer zones (accdg. to Classical Theory): Figure 6. Infant with Anencephaly a. Matrix (ependymal) zone b. Mantle zone Rachischisis c. Marginal zone Severe form of spina bifida Incomplete closure of caudal neuropore (+) defective development of the neural tube Defective development of associated vertebral arches malformation Characteristic features: a. Failure of dorsal portions of the vertebral arches to fuse with each other b. Neural tissue is widely exposed to the surface c. Neural tissue shows considerable overgrowth which Figure 8. Neural tube layer zone becomes necrotic shortly before or after birth a. Matrix (ependymal) zone Lines the enclosed cavity (neurocele) Cells undergoing mitosis produce: a. Neuroblasts (→neurons) b. Spongioblasts (→neuroglial cells) Neuroblasts migrate to the mantle zone (future SC gray matter) & their axons enter the external marginal zone (future SC white matter) Some central processes of DRG ascend in the marginal zone while other synapse with neurns in the mantle zone Once histogenesis is complete, remaining matrix cells differentiate into ependymal cells lining the central canal of your spinal cord or the counterpart in the ventricles of the brain according to the classical theory Figure 7. Congenital anomalies of the NS: Neural tube defects According to Current Theory: - Closed neural tube consists of one cell type: III. DEVELOPMENT OF SPINAL CORD Pluripotent Neuroepithelial cells - Cells form a pseudostratified neuroepithelium Spinal cord develops from caudal elongated part of the - Zonal appearance reflects different phases of their neural tube. proliferative cycle, the sequence being termed During the neural groove stage and immediately after Interkinetic Migration closure of the tube, they divide rapidly, producing more and more neuroepithelial cells. Collectively, they constitute the neuroepithelial layer or neuroepithelium. Page 5 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 Figure 10. Roof and Floor Plate. Figure 9. A transverse section through the developing spinal cord of a human embryo 4 weeks old. (A) A schematic drawing of Development of the Functional Columns the real slide (B). Note the roof or alar plate and the floor or basal 1. Alar Lamina (aka. Alar Plates) plate in (B). - Cells of dorsal region Nerve Cell/ Neuroblast - Afferent or Sensory - Has a round nuclei with dark staining nucleoli - Alar Plates are dorsal thickening, which forms the - Arise from Neuroepithelial Cells as development sensory areas proceeds 2. Basal Lamina (aka. Basal Plates) - Efferent or Motor o Spinal Nerves b. Mantle zone - Formed from Axons of basal lamina that Surrounds Neuroepithelial Layer leave the cord as Ventral Roots joined with Formed by Neuroblasts Peripheral Process of DRG Later forms Gray Matter of the SC - Basal Plates are ventricular thickening, which contains Once the neural tube closes, neuroepithelial cells begin ventral motor horn cells, from motor areas of the spinal to give rise to another cell type characterized by a large cord round nucleus with pale nucleoplasm and a dark- staining nucleolus. These are the primitive nerve cells, NOTE: Cells of both Alar and Basal Laminae are arranged into or neuroblasts. They form the mantle layer, a zone LONGITUDINAL COLUMNS. A longitudinal groove, the sulcus around the neuroepithelial layer. The mantle layer later limitans, marks the boundary between the Alar and Basal forms the gray matter of the spinal cord. Plates. (Sadler, LANGMAN'S MEDICAL EMBRYOLOGY, 2019, p. 315) c. Marginal Zone Columns of the Lamina: Outermost layer of the SC 1. Two (2) AFFERENT columns of ALAR/DORSAL Contains fibers emerging from Neuroblasts in the Mantle LAMINA zone - Receive axons from DRG Myelination of the Nerve Fiber gives Marginal zone a a. General Somatic Afferent column (GSA) WHITE appearance (from the white matter of the SC) - Found throughout the SC - Receives impulses from: NOTE: On x-section: Cavity of the Neural Tube appears like a o Superficial (Cutaneous) Receptors vertical slit. o Deep (Proprioceptive) Receptors b. General Visceral Afferent column (GVA) Formation of the Vertical slit - Found only in: o Thoracolumbar Region Gives dorsal and ventral walls of the Neural Tube a thin o Sacral Region appearance (Roof and Floor Plates) - Receives impulses from: Lateral walls get thickened and demarcated into dorsal and o Viscera ventral regions by SULCUS LIMITANS o Blood Vessels o Sulcus Limitans - inner longitudinal sulcus 2. Two (2) EFFERENT columns of BASAL LAMINA - Gives rise to Motor Fibers a. General Visceral Efferent column (GSE) - Found throughout the SC Page 6 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 -Provides fibers that innervate: - LOWER part of SC ends at eh LOWER BORDER of L1 o Skeletal Muscles Vertebrae - Makes the skeletal muscle to contract - Figure 11. Development of the Spinal Cord on the 8 th b. General Somatic Efferent column (GVE) and 24th week, at Birth and in Adults. c. - Found only in: o Thoracolumbar Region o Sacral Region - Provides Preganglionic Fibers to: o Viscera o Blood Vessels o Glands Figure 12. Development of the Spinal Cord on the 8th and 24th week, at Birth and in Adults. Termination of SC in relation to Vertebral Canal at various stages of development: Nerve Root - From: LUMBAR, SACRAL and COCCYGEAL Figure 11. X-section of a developing SC showing 4 longitudinal - Descends below the Conus Medullaris cell columns. o Conus Medullaris - Lower end of the SC Everything that is in dorsal region will be afferent/sensory - Surrounded by Filum Terminalis columns o Filum Terminalis Everything that is in ventral region will be efferent/motor - Thin thread-like prolongation of Pia mater columns from the tip of Conus Medullaris - Marks the tract of regression of the spinal Positional Changes of the SC cord as well as provides support for the cord (the part covered by dura and 8th week extending from S2 to the coccyx is also - This time, the vertebral canal is filled with spinal cord called coccygeal ligament) - Lengths of SC and Vertebral Column are EQUAL - Forms Cauda Equina (horsetail-like structure in the - SC extends along the entire length of Vertebral Canal spinal canal of subarachnoid space) - Spinal Nerves exit Intervertebral Foramina at the level - Cauda Equina is made up of dorsal and ventral of their origin roots of spinal nerves below the end of the cord at - Intervertebral Foramina DOES NOT remain at the level L2-L3. (Sadler, LANGMAN'S MEDICAL EMBRYOLOGY, of Spinal Nerves 2019, p. 321) - Spinal Nerves are forced to go down and exit in an oblique direction In the third month of development, the spinal cord extends the entire length of the embryo and the spinal nerves pass through the intervertebral foramina at their level of origin. (Sadler, LANGMAN'S MEDICAL EMBRYOLOGY, 2019, p. 320) 24th week - During this time, vertebral column grows more rapidly than the spinal cord - LOWER part of SC ends at S1 Vertebrae At Birth - LOWER part of SC ends at the level of L3 Vertebra In Adults Figure 13. Conus Medullaris. Filum Terminale. Cauda Equina. Page 7 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 IV. DEVELOPMENT OF THE BRAIN Brain - Develops from an enlarged Cranial part of the Neural Tube - Sometimes divided into the: o Brainstem: (direct continuation of spinal cord; has distinct basal (motor) & alar (sensory) plates) ▪ Myelencephalon Figure 14. Primary and Secondary Brain Vesicles. ▪ Pons from Metencephalon ▪ Mesencephalon Differentiation of Prosencephalon into: o Higher Centers: (reflect almost none of this basic pattern, and, instead, show accentuation of the alar a. Telencephalon plates and regression of the basal plates) - Rostral part ▪ Cerebellum - Develops Lateral Diverticula by ▪ Cerebral Hemispheres EVAGINATIONA (Sadler, LANGMAN'S MEDICAL EMBRYOLOGY, 2019, p. 324) - Enlarges, overgrows and covers the Caudal Diencephalon to form CEREVBAL HEMISPHERE End of 4th week b. Diencephalon (Interbrain) Enlarged Cephalic part shows three (3) distinct dilations - Caudal part called: PRIMARY BRAIN VESICLES - Becomes hidden in the lower parts of the Cerebral Hemisphere Cavities form Ventricular System of adult brain - Forms: Thalamus Divided by a groove, hypothalamic sulcus Primary Brain Vesicles: Hypothalamus Epithalamus a. Prosencephalon (Forebrain) c. Mesencephalon b. Mesencephalon (Midbrain) - Gives rise to the MIDBRAIN - 2 groups of motor nuclei in its basal plate: - Not much changes in Early development 1. medial somatic efferent group - Its cavity gets progressively narrowed to form 2. small general visceral efferent group CEREBRAL AQUEDUCT/SYLVIAN - Initially its alar plates appear as 2 longitudinal AQUEDUCT elevations separated by shallow midline d. Rhombencephalon depression. With further development, a transvers - Differentiates into: groove divides each elevation into: o Metencephalon 1. anterior (superior) colliculus - Rostral part 2. posterior (inferior) colliculus (Sadler, LANGMAN'S MEDICAL EMBRYOLOGY, 2019, - Develops into PONS (derived from p. 329) basal plates; pathway for nerve c. Rhombencephalon (Hindbrain) fibers betw SC & cerebral & - consist of the myelencephalon, the most caudal cerebellar cortices) and of the brain vesicles, and the metencephalon, CEREBELLUM (derived from the which extends from the pontine flexure to the alar plates; coordination center for rhombencephalon isthmus (Sadler, LANGMAN'S posture & movement MEDICAL EMBRYOLOGY, 2019, p. 324) (Sadler, LANGMAN'S MEDICAL EMBRYOLOGY, 2019, p. 327) o Myelencephalon 5th week - Caudal part Both the Prosencephalon (Forebrain) and - Gives rise to MEDULLA Rhombencephalon (Hindbrain) subdivide into two (2) OBLONGATA (a transitional zone vesicles producing: FIVE (5) SECONDARY BRAIN between the brain and spinal cord; VESCICLES differs from the SC in that its lateral walls are everted. (Sadler, LANGMAN'S MEDICAL EMBRYOLOGY, 2019, p. 324) Page 8 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 Three (3) Flexures of the Brain b. Median Foramina of Magendie - Folding results to: Primitive brain presents Three (3) flexures: o Flattening of the Rhombencephalon (Hindbrain) a. Pontine Flexure o Buckling effect - At the middle of Rhombencephalon - Displacement of Alar Laminae to lie lateral to (Hindbrain) Basal Laminae b. Convex ventrally Cervical Flexure - Resulting to: - At the junction of the Rhombencephalon o Sensory CN attached laterally to (Hindbrain) and SC Brainstem - Concave ventrally o Motor CN attached medially to - Makes a 90° bend between Brainstem Rhombencephalon (Hindbrain) and SC - Causes the brain to be oriented almost 90° to the SC c. Cephalic (Mesencephalic) Flexure - At the region of Mesencephalon (Midbrain) - Concave ventrally Figure 16. Flexures of the Brain. 2. Cervical Flexure - Concave ventrally; Convex dorsally - Appears at the junction of the Rhombencephalon Figure 15. Flexures of the Brain. (Hindbrain) and SC 3. Cephalic Flexure 1. Pontine Flexure - Concave ventrally; Convex dorsally - Rhombencephalon (Hindbrain) folds at its middle - Appears at the level of Midbrain - Forms an acute angle ventrally 4th ventricle - Cavity that formed from folding of the Rhombencephalon (Hindbrain) - This foramina makes the CSF flow continuously inside and outside of brain and spinal cord - Diamond-shaped space - Widest at line of folding (Jxn of PONS and MEDULLA) - Tapers Superiorly to the narrow canal of Midbrain (AQUIDUCT OD SYLVIUS) Figure 17. Primary and Secondary Brain Vesicles and Adult - Tapers Inferiorly to the central canal on the lower Derivatives. part of Medulla - Thin roof is pulled out to cover the space posteriorly - - Thin roof breaks down forming Apertures through which the cavity of Neural Tube communicates with the surrounding SAS: a. Lateral Foramina of Luschka Page 9 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 DEVELOPMENT OF VENTRICULAR SYSTEM c. 4th Ventricle - Continuous with central canal of SC which presents Cavities of brain vesicles form the Ventricular System of TERMINAL VENTRICLE the adult brain Terminal Ventricle - Small dilation at the inferior end Cerebrospinal fluid (CSF) - Formed in the Ventricles - Mainly in the lateral Ventricles by the Choroid Plexuses - Leaves the Ventricular System into SAS (Subarachnoid space) around the Brain and SC through the Foramina of Magendie and Luschka - 400-500 mL of CSF per day - CSF “floats” the brain and, thus provides cushion for the brain and gives its buoyancy so that its weight does not compress cranial nerves against the inside of the skull (Sadler, LANGMAN'S MEDICAL EMBRYOLOGY, 2019, pp. 335,336) Figure 18. Ventricular System of the Brain. - Lateral ventricle (right and left) goes to the 3rd ventricle in the diencephalon by interventricular foramen of Monroe. - The 3rd ventricle will in communication with 4th ventricle in the brainstem by the cerebral aqueduct (of sylvius). - After 4th ventricle, there is two pores or foramina, the medial and lateral foramina, Magendie and Lushka respectively. So that, the CSF will flow inside of the brain and spinal cord as well as in the subarachnoid space around brain and spinal cord. Cavities of the Brain Vesicle Figure 19. Four (4) Ventricles of the Brain. Cavity Becomes VI. CLINICAL CORRELATES Rhombencephalon 4th Ventricle (Hindbrain) cavity Hydrocephalus Narrow Cerebral Aqueduct Mesencephalic cavity (Aqueduct of Sylvius) clinical condition characterized by dilatation of ventricles due to excess accumulation of CSF within them. In most Diencephalic cavity 3rd Ventricle cases, hydrocephalus in the newborn is due to an Twin Telencephalic Lateral ventricle obstruction of the aqueduct of Sylvius (aqueductal Cavities stenosis). This prevents the CSF of the lateral and third ventricles from passing into the fourth venricle and from Four (4) Ventricles of the Brain there into the subarachnoid space, where it would be resorbed. a. Two (2) Lateral Ventricles occurs either due to overproduction of CSF or - Communicates with the 3rd ventricle via obstruction to its circulation, or there is failure of INTRAVENTRICULAR FORAMINA (Foramen of reabsorption of the CSF Monro) features: fluid accumulates in the lateral ventricles and b. 3rd Ventricle presses on the brain and bones of the skull. Because - Communicates with the 4th ventricle via CEREBRAL the cranial sutures have not yet fused, spaces between AQUEDUCT (Aqueduct of Sylvius) them widen as the head expands. In extreme cases, Page 10 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 brain tissue and bones become thin and the head may sulcus present in each lateral wall of the be very large diencephalon o “setting-sun” appearance of the eyes appears to be rostral continuation of sulcus o disproportionately large size head limitans divides lateral wall into dorsal (THALAMUS) and ventral regions (HYPOTHALAMUS) b. Neurohypophysis downgrowth from the floor of the anterior hypothalamus joins an upgrowth from the stomodeum (ADENOHYPOPHYSIS) to form HYPOPHYSIS CEREBRI (PITUITARY GLAND) Dandy-Walker Syndrome due to atresia and blockage of the apertures (foramina of Luschka and Magendie) in the roof of 4th ventricle syndrome consists of the following o dilatation of 4th ventricle (black area in the MRI of the patient) o agenesis of cerebellar vermis or the mid area of your cerebellum o occipital meningocele o agenesis of the splenium of corpus callosum instead of a hardened body like your corpus Figure 21. Forebrain (Prosencephalon). callosum, it is filled with CSF c. Epithalamus comprising pineal gland and habenular nuclei develops posteriorly in the roof plate d. Pineal Gland grows posteriorly from the roof plate at its Figure 20. Dandy-Walker syndrome. junction with the midbrain lies on the dorsal surface of midbrain VII. PRIMARY BRAIN VESICLES between the two superior colliculi 2. Telencephalon consists of a median part and two lateral Prosencephalon (Forebrain) diverticular or cerebral vesicles MEDIAN PART 1. Diencephalon o forms a small anterior part of the 3rd ventricle develops from the median portion of the and lamina terminalis prosencephalon The Telencephalon is over the diencephalon. The Telencephalon has its cavity called 3RD VENTRICLE is your cerebral hemispheres consists of two thick lateral walls, a thin roof and floor plates a. Hypothalamic Sulcus Page 11 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 above the choroid fissure, the medial wall of the hemisphere thickens to from HIPPOCAMPUS that will be part of your limbic system subsequent massive expansion of the cerebral hemispheres (neocortex), the hippocampus is displaced postero-inferiorly into the lateral ventricle FORNIX is drawn out as an efferent tract on its medial aspect choroid fissure also becomes curved, interposed Figure 22. Telencephalon. between the fornix and diencephalon c. CORPUS STRIATUM part of the basal ganglia develops bilaterally in the floor of telencephalon adjacent to thalami these areas of gray matter are sensory- motor control centers major pathway that developed for descending fibers from the cerebral cortex and ascending fibers from the thalamus fibers (INTERNAL CAPSULE) form on each side divide the corpus striatum into two parts: o dorsomedial portion (CAUDATE Figure 23. Telencephalon. NUCLEUS) o ventrolateral portion (LENTIFORM a. LAMINA TERMINALIS NUCLEUS) represents the cephalic end of the primitive neural tube d. THREE MENINGES / MEMBRANES corresponds with the closure of anterior PIA MATER neuropore o leptomeninges o derived from neural crest b. LATERAL DIVERTICULA ARACHNOID MATER represent rudiments of cerebral hemispheres o leptomeninges cavities of hemispheres (lateral ventricles) o derived from neural crest communicate with the cavity of diencephalon DURA MATER (3rd ventricle) through the interventricular o derived from mesenchyme foramen of Monro surrounding the neural tube Neural Tube Defects developing cerebral hemisphere enlarges forward, ◦ Most defects of the spinal cord result from abnormal upward and backward in that order so that it will closure of the neural folds in the third and fourth weeks of cover the diencephalon or the thalamus development. as the vesicle grows backward it overlaps ◦ may ínvolve the meninges, vertebrae, muscles, and successively diencephalon, mesencephalon and skin. cerebellar rudiments ◦ The birth prevalence of NTDs, including spina bifida and lowest parts of medial walls of hemispheres remain anencephaly, varies among different populations and may be as very thin due to disproportionate growth of various high as 1/200 births in some areas, such as Northern China. parts of the hemispheres ◦ The birth prevalence of NTDs in the United States has decreased by approximately 25% to 1/1,500 births since choroid plexus of 3rd ventricle protrudes laterally fortificatíon of flour with folic acid was instituted in 1998. through this thin wall into the lateral ventricle along a line (CHOROID FISSURE) Spina bifida Page 12 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 ◦ is a general term for NTDs affecting the spinal región. It consists of a spiitting of the vertebral arches and may or may not involve underiying neural tissue. Mesencephalon (Midbrain) most primitive of the brain vesicles generally retains a cylindrical form its narrowed cavity forms the cerebral aqueduct, which is continuous below with the 4th ventricle and above the 3rd ventricle during the 1 month of the embryo, we have the midbrain and it will not differentiate like your prosencephalon and rhombencephalon anterior to the cerebral aqueduct, the basal laminae give rise to TEGMENTUM and SUBSTANTIA NIGRA 1. CRUS CEREBRI formed from the enlargement of the marginal layer of each basal lamina Spina bifida occulta serve as pathways for nerve fibers descending from is a defect in the vertebral arches that is covered by skin the cerebral cortex to the lower centers in pons, and norm ally does not involve underlying neural tíssue medulla and spinal cord Most often, the defect occurs in the sacral región [S1- S2) and is sometímes marked by a patch of hair overlying the affected región. The defect, which is due to a lack of fusión of the vertebral arches, affects about 10% of otherwise normal people. The malformatíon is not usually detected at birth and dees not cause disability. Often, the defect is first notíced as an incidental find- ing diagnosed when an x-ray of the back is performed. meningocele oniy fluid-filled meninges protrude through the defect myelomeningocele neural tissue is included in the sac Figure 24. Midbrain (Mesencephalon). spina bifida with myeloschisis or rachischisis the neural folds do not elevate but remain as a flattened mass of neural tissue cells of alar laminae invade the roof plate to from bilateral longitudinal elevations separated by a shallow midline groove each elevation is subdivided by a transverse groove into Hydrocephaly upper and lower parts called SUPERIOR and requiring intervention develops in 80% to 90% of INFERIOR COLLICULI children born w ith severe NTDs 2. CORPORA QUADRIGEMINA Arnold-Chiari malformation four colliculi (CORPORA QUADRIGEMINA) herniation of part of the cerebellum into the foramen Corpora= bodies, quadrigemina= four develop into magnumj, which obstructs the flow of cerebrospinal fluid and causes the hydrocephalus. the roof plate dorsal to the aqueduct of Sylvius and Herniation of the cerebellum occurs because the spinal from TECTUM cord is tethered to the vertebral column due to its abnormal from these four colliculi, we have the superior and development. inferior colliculi As the vertebral column lengthens, tethering of the cord pulís the cerebellum into the foramen magnum, cutting off the flow of cerebrospinal fluid. Hydrocephalus can be treated by inserting a ventriculoperitoneal shunt, which allows drainage of the cerebro-spinal fluid from one of the cerebral ventricles to the peritoneal cavity. Page 13 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 nuclei are arranged in longitudinal columns each lamina contains two columns (somatic and visceral) but in the brainstem: o special branchial columns appears between somatic and visceral columns of each lamina o special somatic column appears in the most lateral part of the alar lamina to receive impulses of special sensations of hearing and balance o basal lamina has three columns and alar lamina has four columns Figure 25. Corpora quadrigemina of tectum. Rhombencephalon (Hindbrain) 1. Developing 4th Ventricle caudal part of myelencephalon (rostral part is the metencephalon) has a central canal and forms the closed part of medulla rostrally the central canal expands as the cavity of the 4th ventricle floor of 4th ventricle is derived from myelencephalon (medulla) and metencephalon (pons) on either side of midline, the floor consists of the basal The Pia mater will contribute in formation of your choroid plexus and alar laminae, which are separated from each other that will invaginate in the cavity of your 4 th ventricle. This choroid by a longitudinal sulcus called SULCUS LIMITANS plexus will manufacture CSF Figure 27. Developing fourth ventricle and cerebellum. (MS = median sulcus, SL = sulcus limitans) NOTE: a. Vascular pia mater invaginates ependyma to form choroid plexus b. Alar lamina lies lateral to basal lamina, and c. Rhombic lips derived from alar laminae grow together to form cerebellum dorsal to the roof of fourth ventricle Figure 26. Posterior view of developing rhombencephalon 2. Functional Columns of Gray Matter in the Brainstem showing the role of pontine flexure in the formation of fourth a. Functional Column in the Basal Lamina of ventricle. Brainstem Page 14 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 Somatic Efferent (SE) known as PONS conduit or passageway of Special Visceral Efferent (SVE) descending as well as ascending impulses from General Visceral Efferent (GVE) different fibers from the brain to the spinal cord to b. Functional Columns in the Alar Lamina of the cerebellum, and from the spinal cord going up Brainstem the cerebellum and the brain General Visceral Afferent (GVA) Special Visceral Afferent (SVA) VIII. CLINICAL CORRELATES General Somatic Afferent (GSA) Special Somatic Afferent (SSA) mitotic activity within the neural tissue is completed during prenatal development all motor nuclei of the brainstem are derived thus, a person is born with all neuron he was destined to from functional columns of its basal plate have all sensory nuclei of the brainstem are derived however the nervous tissue continues to grow and from functional columns of the alar plate specializes even after birth, particularly in initial several years of postnatal life Pheochromocytomas ◦ rare tumors involving chromaffin cells that result in excessive production and release of epinephrine and norepinephrine causing paroxysmal episodes of hypertension, increased heart rate, headaches, and other associated symptoms. ◦ Most occur in the adrenal medulla, but approximately 10% occur in other sites, usually the abdomen. ◦ Twenty-five percent are familial and have been associated with mutations in the RETgene that plays a role in neural crest cell migration. Figure 28. Functional columns of gray matter in the brainstem. 3. Roof of 4th Ventricle, Tela Choroidea, Choroid Plexus, Congenital Megacolon (Hirschsprung Disease) Rhombic Lips ◦ results from a failure of parasympathetic ganglia to form a. Roof of 4th Ventricle in the wall of a part or all of the colon and rectum because the consists of a single layer of ependymal cells neural crest cells fail to migrate. covered by a vascular mesenchyme (pia ◦ Most familial cases of Hirschsprung disease are caused mater) by m utations in the RETgene, which codes for a cell membrane b. Tela Choroidea tyrosine kinase receptor. This gene on chromosome lOqll is consists of pia mater along with the covering essential for neural crest cell migration. The ligand for the recep- layer of ependymal cells t o r is GLIAL CELL-DERIVED NEUROTROPHIC GROWTH c. Choroid Plexus FACTOR secreted by mesenchym e cells through which crest sac-like invaginations consisting of tela cells migrate. Receptor ligand interactions then regúlate crest cell migration. choroidea and tuft or bunch of capillaries ◦ Consequently, if there are abnormalities in the receptor, due to active proliferation of vascular igration is inhibited, and no parasympathetic ganglia form in mesenchyme affected areas. The rectum is involved in nearly all cases, and d. Rhombic Lips the rectum and sigmoid are involved in 80% of affected infants. formed from the dorsolateral parts of the alar The transverse and ascending portions of the colon are involved laminae of metencephalon in only 10% to 20%. The colon is dilated above the affected extend medially and dorsally región, which has a small diameter because of tonic contraction these meet and fuse in the midline over the of noninnervated musculature. roof of the 4th ventricle and then grow dorsally to form the CEREBELLUM Hypophyseal Defects 4. Pons marginal layer of basal plates of metencephalon Occasíonally,a small portion of Rathke’s pouch persists expands as a bridge for nerve fibers connecting in the roof of the pharynx as a pha ryngeal cerebral cortex and cerebellar cortex (CORTICO- hypophysis. Craniopharyngiomas arise from rem PONTOCEREBELLAR PATHWAYS), later be nants of Rathke’s pouch. They may form within the sella Page 15 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 turcica or along the stalk of the pituitary but usually lie IX. TEST YOUR KNOWLDEGDE above the sella. They may cause hydrocephalus and pituitary dysfunction (e.g., diabetes insipidus, growth 1. The following are the structures of the neural ectoderm failure). except: Microcephaly A. Neural Tube to become the CNS ◦ describes a cranial vault that is smaller than normal B. Neural Crest cells to become PNS ◦ Because the size of the cranium depends on growth of C. Ectodermal Placode to become Cranial nerves the brain, the underiying defect is in brain development. Causation of the abnormality is varied; it m ay be genetic D. Endodermal Placode to become the ANS (autosomal recessive] or caused by prenatal insults, such as infection or exposure to drugs or other teratogens. Intellectual 2. Ectoderm refers only to the neural plate region of the disability occurs in more than half the cases. trilaminar embryo A. True B. False 3. The central nervous system forms in the sequence: A. notochord to neural plate to neural tube B. neural tube to neural plate to neural groove C. neural plate to neural groove to neural tube D. neural plate to neural crest to neural zone 4. The neural plate is narrower at the caudal (tail) end and therefore closes earlier than the broad cranial (head) end. A. True B. False 5. The correct sequence from cranial to caudal of the Exencephaly secondary brain vesicles is: ◦ failure of the cephalic part of the neural tube to cióse. A. telencephalon, diencephalon, metencephalon, ◦ the vault of the skuli does not form, leaving the mesencephalon, myelencephalon malformed brain exposed. Later, this tissue degenerates, leaving B. telencephalon, diencephalon, mesencephalon, a mass of necrotic tissue. This defect is called anencephaly, metencephalon, myelencephalon aithough the brain stem remains intact C. prosencephalon, diencephalon, mesencephalon, ◦ the closure defect of the neural tube extends caudally into the spinal cord, and the abnormality is called craniorachis- myelencephalon, metencephalon chisís D. prosencephalon, mesencephalon, metencephalon, ◦ there is anenceph-aly but with a large defect involving myelencephalon, rhombencephalon the spine. Because anencephalic fetuses lack a swallow- ing reflex, the last 2 months of pregnancy are characterized by 6.___________are established by a process in which a polyhydramnios. The abnor-mality can be recognized on developing axon is attracted towards the midline by a ultrasound, as the vault of the skuli is absent. Anencephaly gradient of a diffusible attractant molecule. occurs in 1per 5,000 births and is more common in females than A. Degradation in males. Like spina bifida, many of these cases can be B. Diffusion prevented by having women take 400 micro grams of folie acid C. Decussations per day before and during early pregnancy. D. Delineation 7. At ____ spinal cord and vertebral column are equal A. 24th week B. 8th week C. At birth D. During adult 8. This is the folding to flattening of the Hindbrain. A. Buckle Effect B. Buckling Effect C. Roofing effect D. Duckling Effect Page 16 of 17 CMED 1D  (008) EMBRYOLOGIC DEVELOPMENT OF CENTRAL NERVOUS SYSTEM DR. STEVE ARELLANO| 02/01/21 D. Foramen of Monreo 9. Morphogenesis comprise of all but one: 20. CSF is mainly formed in the _____ Ventricle/s by the A. Cell division _____. B. Differentiation A. A.Lateral Ventricles; Choroid Plexus C. Projection B. B.Third Ventricle; Cerebral Aqueduct D. Apoptosis C. C.Fourth Ventricle; Aqueduct of Sylvius D. D.Lateral Ventricles; Interventricular Foramen11. 10. Dandy Walker is the atresia of Luschka and Magendie having all but one signs: ANSWER KEY. A. Dilatation of 4th ventricle [1.D] [2.T ] [3.C ] [4.F ] [5.B ] B. Genesis of cerebral vermis [6. C] [7. B] [8.B ] [9. C] [10. B] [11. T] [12.F ] [13.F ] [14.F ] [15.F ] C. Occipital Meningocele [16. B] [17.C ] [18.D ] [19.A ] [20.A ] D. Agenesis of splenium of Corpus Callosum REFERENCES 11. True or False: The nervous system is derived from ectoderm except blood vessels and neuroglial elements 1. Doc Steve Arellano PPT 12. True or False: Neurulation happens on the 15th day 2. Sadler,T. (2019). LANGMAN'S MEDICAL EMBRYOLOGY (14th ed.). Wolters Kluwer. 13. True or False: The mantle zone is where the white matter of the spinal cord is derived. 3. Sadler, T. (n.d.). LANGMAN'S MEDICAL EMBRYOLOGY (13th ed.). Wolters Kluwer. 14. True or False: The marginal zone is where the gray matter of the spinal cord is derived. 15. True or False: The clinical division of the prenatal period is divided into 3 stages 16. The dorsal thickening, which forms the sensory areas. A. Basal Lamina B. Alar Lamina C. Ventral Lamina D. Sulcus Limitans 17. Formed from Axons of basal lamina that leave the cord as Ventral Roots joined with Peripheral Process of DRG A. Central Cana B. Dorsal Root Ganglion C. Spinal Nerves D. Alar Plates 18. During this time, the lower part of SC ends at S1 Vertebrae and the vertebral column grows more rapidly than the spinal cord. A. 24th day B. 24th month C. 24th hour D. 24th week 19. A diamond-shaped space which is formed from folding of the Rhombencephalon (Hindbrain). A. Fourth Ventricle B. Third Ventricle C. Lateral Ventricles Page 17 of 17 CMED 1D