Development of the Nervous System (Dr. Mohd Asim Khan) PDF

DEVELOPMENT OF THE NERVOUS SYSTEM MOHD ASIM KHAN [email protected]...

DEVELOPMENT OF THE NERVOUS SYSTEM MOHD ASIM KHAN [email protected] LEARNING OBJECTIVES At the end of this lecture, the students should be able to: 1. Describe the development of the neural tube, including the stages of development and the adult derivatives of each brain vesicle 2. Trace the lineage of the cells of the neural tube wall, including the alar and basal plates 3. Identify the derivatives of the neural crest 4. Describe the development of the pituitary (hypophysis) 5. List and characterize major congenital malformations of the central nervous system Drawings by: Medical Student, Al Samir Campus (KKU-KSA) (Reproduced with permission from the author)  NERVOUS SYSTEM ▪ The nervous system consists of three main parts: A B 1. CENTRAL NERVOUS SYSTEM (CNS) ▪ Consists of: * Brain and Spinal cord 2. PERIPHERAL NERVOUS SYSTEM (PNS) ▪ Consists of: * Cranial and Spinal nerves & their associated ganglia 3. AUTONOMIC NERVOUS SYSTEM (ANS) ▪ Has parts in both the CNS and PNS ▪ Consists of neurons that innervate 1. Smooth muscles 2. Cardiac muscle 3. Glandular epithelium ▪ Divided into two parts: 1. Sympathetic A: Central Nervous System B: Peripheral Nervous System 2. Parasympathetic Reference: Clinical Neuroanatomy by Snell, 7th edition  DEVELOPMENT OF THE NERVOUS SYSTEM ▪ CENTRAL NERVOUS SYSTEM (CNS) 1. CNS is formed in week 3 of human development, during which time the neural plate develops 2. The neural plate, consisting of neuroectoderm, becomes the neural tube, which gives rise to the brain and spinal cord ▪ PERIPHERAL NERVOUS SYSTEM (PNS) ▪ Derived from three sources: 1. Neural crest cells 2. Neural tube - Gives rise to all preganglionic autonomic nerves (sympathetic and parasympathetic) - All nerves (alpha-motoneurons and gamma-motoneurons) that innervate skeletal muscles 3. Mesoderm - Gives rise to the dura mater and to connective tissue investments of peripheral nerve fibers (endoneurium, perineurium, and epineurium) Reference: Board Review Series-Embryology By Dudek, 5th Edition  DEVELOPMENT OF THE NEURAL TUBE Formation of the neural plate CNS IS FORMED IN WEEK 3 OF HUMAN DEVELOPMENT ▪ NEURAL TUBE: Gives rise to the central nervous system (brain & spinal cord) ▪ NEURAL PLATE: 1. Thickened area of embryonic ectoderm (neuroectoderm) 2. Develops central nervous system ▪ NEURULATION: - Refers to the formation of the neural plate and neural tube Neurulation Neurulation Reference: Netter’s Atlas of Human Embryology, By Cochard, 1st edition  DEVELOPMENT OF THE NEURAL TUBE ▪ EVENTS OF NEURULATION 1. The notochord and paraxial mesoderm induce the overlying ectoderm to differentiate into the neural plate 2. The lateral edges of the neural plate elevate to form the neural folds Formation of the neural plate Development of the neural tube and crest Reference: Netter’s Atlas of Human Embryology, By Cochard, 1st edition Reference: High-Yield Neuroanatomy, By Gould, 5th edition  DEVELOPMENT OF THE NEURAL TUBE ▪ EVENTS OF NEURULATION 3. The fusion of the neural folds proceeds in cranial and caudal directions and give rise to the neural tube 4. The open ends of the neural tube form the cranial (rostral) and caudal neuropores 5. The cranial and caudal neuropores connect the lumen of the neural tube with the amniotic cavity Dorsal view of an embryo at day 23 Dorsal view of the neural tube Reference: Medical Embryology by Langman, 9th Edition Reference: Before we are Born- Essentials of Embryology and Birth Defects, By Moore, 8th Edition Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4 th edition  DEVELOPMENT OF THE NEURAL TUBE ▪ EVENTS OF NEURULATION 1. The cranial neuropore closes during day 25 and becomes the lamina terminalis of the brain 2. The caudal neuropore closes during day 27 SAUDI ARABIA: KINGDOM OF HUMANITY Mnemonic device (‫)اليوم الوطني للمملكة العربية السعودية‬ Saudi National Day= 23rd September Number of neuropores=2 A B 23+2=25; 25+2=27 A: Lateral view of an embryo at approximately 24 days neuro-: nervous system B: Lateral view of an embryo at approximately 27 days pore: passage Lamina terminalis Reference: Before we are Born- Essentials of Embryology and Birth Defects, By Moore, 8th Edition Reference: The human brain: An introduction to its functional anatomy By Nolte, 6thedition  DEVELOPMENT OF THE NEURAL TUBE 1 2 ▪ EVENTS OF NEURULATION 6. As the neural plate folds, some cells differentiate into neural crest cells 7. The cranial part of the neural tube becomes the adult brain 8. The caudal part of the neural tube becomes the adult spinal cord 9. The lumen of the neural tube gives rise NEURAL CREST to the ventricular system of the brain and central canal of the spinal cord MNEMONIC DEVICE Please = P = Plate (Neural) Go = G = Groove (Neural) NEURULATION First = F = Fold (Neural) To = T = Tube (Neural) Class = C = Crest (Neural) 1. Reference: Basic Clinical Neuroscience, By Young & Tolbert, 3rd edition 2. Reference: Netter’s Atlas of Human Embryology, By Cochard, 1st edition  DERIVATIVES OF THE NEURAL CREST Derivatives of the germ layer Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4th edition Reference: Before we are Born- Essentials of Embryology and Birth Defects, By Moore, 8th Edition  DEVELOPMENT OF THE BRAIN ▪ During week 4, the neural tube gives rise to three primary vesicles from rostral to caudal 1. PROSENCEPHALON 2. MESENCEPHALON 3. RHOMBENCEPHALON ▪ During week 5, there are five secondary vesicles Vesicle: A pocket of embryonic tissue that is the beginning of an organ ▪ The three primary vesicles are not arranged in a straight line and are associated with two bends or flexures BRAIN FLEXURES DESCRIPTION 1. CERVICAL - Concave ventrally; Occurs between the rhombencephalon and spinal cord 2. CEPHALIC (MESENCEPHALIC) - Concave ventrally; Occurs at the level of mesencephalon PONTINE FLEXURE - Concave dorsally; Associated with secondary vesicle - Divides the hindbrain into the myelencephalon caudally and the metencephalon rostrally Dorsal A B Flexure: A bent or curved part A: Primary vesicles during the 4th week B: Secondary vesicles during the 5th week Ventral Reference: The human brain: An introduction to its functional anatomy By Nolte, 6thedition  DEVELOPMENT OF THE BRAIN PRIMARY BRAIN VESICLE DESCRIPTION 1. PROSENCEPHALON ▪ proso= Greek, forwards + enkephalos, brain (forebrain) ▪ Most rostral primary brain vesicle that gives rise to diencephalon and telencephalon 2. MESENCEPHALON ▪ mes= Greek, middle + enkephalos, brain (midbrain) ▪ Midbrain portion of the developing brainstem 3. RHOMBENCEPHALON ▪ rhomb=Greek, rhombus + enkephalos, brain (hindbrain) ▪ Divides into the metencephalon and myelencephalon Diamond Rhombus BRAIN VESCLES Kabsa (Rice) BRAIN VESCLES Please Move Rice Reference: Clinical Neuroanatomy by Snell, 7th edition  DEVELOPMENT OF THE BRAIN PRIMARY BRAIN VESICLE SECONDARY BRAIN VESICLE DESCRIPTION 1. PROSENCEPHALON ▪ TELENCEPHALON ▪ Greek: telos, ‘end’ + enkephalos ‘brain’ (End-brain) ▪ DIENCEPHALON ▪ Greek: dia, ‘through’ + enkephalos ‘brain’ (Between-brain) 2. MESENCEPHALON ▪ MESENCEPHALON ▪ Greek: mes, ‘middle’ + enkephalos, brain 3. RHOMBENCEPHALON ▪ METENCEPHALON ▪ Greek: meta, ‘behind or after’ + enkephalos, brain ▪ MYELENCEPHALON ▪ Greek: myelos, “marrow, medulla” + enkephalos, brain MNEMONIC DEVICE PROSENCEPHALON = P = PRE TELENCEPHALON = T = TERM DIENCEPHALON = D = DELIVERY PRIMARY BRAIN VESCICLE SECONDARY BRAIN VESICLE Reference: The human brain: An introduction to its functional anatomy By Nolte, 6thedition  DEVELOPMENT OF THE BRAIN ▪ The forebrain (PROSENCEPHALON) partially divides into two secondary brain vesicles: 1. TELENCEPHALON 2. DIENCEPHALON ▪ The midbrain (MESENCEPHALON) does not divide ▪ The hindbrain (RHOMBENCEPHALON) divides into two secondary brain vesicles: 1. METENCEPHALON 2. MYELENCEPHALON Reference: Before we are Born- Essentials of Embryology and Birth Defects, By Moore, 8th Edition  DEVELOPMENT OF THE BRAIN A B A: Primary vesicles during the 4th week B: Secondary vesicles during the 5th week MNEMONIC DEVICE WEEK VESICLE 4 3 (Primary vesicle) 5 5 (Secondary vesicle) Reference: The human brain: An introduction to its functional anatomy By Nolte, 6thedition  FUNDAMENTAL CROSS-SECTIONAL ORGANIZATION OF THE DEVELOPING NEURAL TUBE ▪ The brainstem and spinal cord are composed of plates separated by the sulcus limitans ▪ The sulcus limitans separates the future sensory and motor areas 1. An alar plate: Gives rise to sensory neurons 2. A basal plate: Gives rise to motor neurons 3. Interneurons: Are derived from both plates Dorsal/Posterior Ventral/Anterior Motor- Anterior/Ventral We sit in the front to drive motor car Major regions in cross sections of the neural tube The brainstem showing the cell columns derived from the alar and basal plates Reference: Human Embryology and Developmental Biology, By Carlson, 3rd Edition Reference: High-Yield Neuroanatomy, By Gould, 5th edition FUNDAMENTAL CROSS-SECTIONAL ORGANIZATION OF THE DEVELOPING NEURAL TUBE Major regions in cross-sections of the neural tube (A) and spinal cord (B) Reference: Medical Embryology by Langman, 9th Edition KING KHALID UNIVERSITY, ABHA, KSA MNEMONIC DEVICE ALAR = A = ASIAN SENSORY = S = SCHOOL OF Motor- Anterior/Ventral BASAL = B = BUSINESS We sit in the front to drive MOTOR = M = MANAGEMENT motor car  MYELINATION ▪ Myelination begins in the fourth month of the gestation 1. MYELINATION OF CENTRAL NERVOUS SYSTEM (CNS) 1. Accomplished by OLIGODENDROCYTES 2. MYELINATION OF PERIPHERAL NERVOUS SYSTEM (PNS) 2. Accomplished by SCHWANN CELLS A: Diagrammatic representation of myelinated fiber in peripheral nerves B: Diagrammatic representation of unmyelinated fiber in peripheral nerves Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4 th edition Myelination in the CNS (right) and PNS (left) Reference: Human Embryology and Developmental Biology, By Carlson, 3rd Edition  THE HYPOPHYSIS (PITUITARY GLAND) DERIVED FROM TWO EMBRYOLOGIC SUBSTRATA DEVELOPMENT OF THE PITUITARY GLAND Reference: Before we are Born- Essentials of Embryology and Birth Defects, By Moore, 8th Edition THE HYPOPHYSIS (PITUITARY GLAND) Development of the pituitary gland (A-F) IMPORTANT ▪ Remnants of Rathke pouch may give rise to a congenital cystic tumor, a CRANIOPHARYNGIOMA Reference: Human Embryology, By Larsen, 5th edition  NEURAL TUBE DEFECTS (NTDs) Mnemonic device (‫)اليوم الوطني للمملكة العربية السعودية‬ Saudi National Day= 23rd September Number of neuropores=2 23+2=25; 25+2=27 CAUSES OF NTDs 1. Genetic 2. Nutritional 3. Environmental ▪ Folic acid supplements taken during 1st trimester reduce the incidence of NTDs UPPER NEURAL TUBE DEFECT LOWER NEURAL TUBE DEFECT ▪ Cranial (rostral, anterior) neuropore ▪ Caudal (posterior) neuropore Reference: Color Atlas of Clinical Embryology, By Moore, 2nd Edition  CONGENITAL ANOMALIES OF THE UPPER NEURAL TUBE DEFECT NEURAL TUBE DEFECT TERMINOLOGY ENCEPHALOCELE ▪ encephal/o= brain + -cele= hernia, swelling MENINGOCELE ▪ meningo= meninges + -cele= hernia, swelling MENINGOENCEPHALOCELE ▪ meningo= meninges + encephal/o= brain + -cele= hernia, swelling MENINGOHYDROENCEPHALOCELE ▪ meningo= meninges + hydor= water + encephal/o= brain + -cele= hernia, swelling OCCIPITAL ENCEPHALOCELE Only meninges Only meninges+brain Only meninges+brain+part of ventricular system Fig.1 Fig.2 Fig.3 Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4th edition  CONGENITAL ANOMALIES OF THE UPPER NEURAL TUBE DEFECT NEURAL TUBE DEFECT EMBRYOLOGICAL BASIS ENCEPHALOCELE Crannim - Herniation of intracranial contents through a defect in the cranium MENINGOCELE Skull - Occurs when the meninges project through the skull defect MENINGOENCEPHALOCELE Skull - Occurs when the meninges and brain project through the skull defect MENINGOHYDROENCEPHALOCELE - Occurs when the meninges, brain, and a portion of the ventricle protrude Skull through the skull defect OCCIPITAL ENCEPHALOCELE Only meninges Only meninges+brain Only meninges+brain+part of ventricular system Fig.1 Fig.2 Fig.3 Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4th edition  ENCEPHALOCELE IMPORTANT 1. Alpha-fetoprotein (AFP) is found in the amniotic fluid and maternal serum 2. It is an indicator of neural tube defects (e.g., spina bifida, anencephaly) 3. AFP levels are reduced in mothers of fetuses with Down Syndrome Reference: Netter’s Atlas of Human Embryology, By Cochard, 1st edition  CONGENITAL ANOMALIES OF THE UPPER NEURAL TUBE DEFECT NEURAL TUBE DEFECT EMBRYOLOGICAL BASIS ANENCEPHALY - Failure of the rostral neuropore to close during the 4th week of development results in an-: lack of; without failure of the skull and the underlying brain to properly develop encephalo-: brain - Although it is commonly called anencephaly (meaning without the brain), the term meroanencephaly (meaning without part of the brain) is actually more accurate because mero-: partly or partial the brainstem may be fairly intact, but the forebrain and cerebellum are largely absent - Not compatible with life Fig.1 Fig.2 Reference: Netter’s Atlas of Human Embryology, By Cochard, 1st edition Reference: Medical Embryology by Langman, 9th Edition  CONGENITAL ANOMALIES OF THE UPPER NEURAL TUBE DEFECT NEURAL TUBE DEFECT EMBRYOLOGICAL BASIS HOLOPROSENCEPHALY - Results from failure of midline cleavage of the embryonic brain (prosencephalon) Greek, holos, ‘whole’ - The telencephalon contains a singular ventricular cavity proso, ‘forward’ - Associated with a number of environmental exposures, including alcohol, retinoic acid, enképhalos, ‘brain’ and maternal diabetes It is a condition of a whole (inappropriately divided) forebrain The sequence of events by which the primitive prosencephalon differentiates into the diencephalic and telencephalic vesicles is called prosencephalization A: Alobar holoprosencephaly: NO LOBES DEVELOP B: Semilobar holoprosencephaly: SOME SEPARATION OF FORBRAIN INTO TWO LOBES Division of prosencephalon Reference: The human brain: An introduction to its functional anatomy By Nolte, 6 thedition Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4th edition  CONGENITAL ANOMALIES OF THE LOWER NEURAL TUBE DEFECT NEURAL TUBE DEFECT EMBRYOLOGICAL BASIS SPINA BIFIDA OCCULTA - Results from failure of the embryonic halves of the neural arch (vertebral arch) to grow normally Spina= Latin,’spine’ and fuse in the median plane Bifida= Latin,’split’ - Occurs in 5th lumbar or 1st sacral in approximately 10% of otherwise normal people Occulta= Latin,’hidden’ - Usually produces no clinical symptoms - Physical examination shows small dimple with a tuft of hair arising from it ▪ The defect in spina bifida occulta is not visible ▪ There is no opening or sac on the back but small gap in the spine 1 2 3 SPINA BIFIDA OCCULTA 1. Reference: Netter’s Atlas of Human Embryology, By Cochard, 1st edition 2. Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4th edition 3. Reference: Before we are Born- Essentials of Embryology and Birth Defects, By Moore, 8th Edition  CONGENITAL ANOMALIES OF THE LOWER NEURAL TUBE DEFECT ▪ SPINA BIFIDA CYSTICA SPINA BIFIDA APERTA aperta=open 1. SPINA BIFIDA WITH MENINGOCELE 1. Skin is not closed over the vertebral defect 2. SPINA BIFIDA WITH MENINGOMYELOCELE 2. Patent (open) aperture is present Note: (1) and (2) are referred collectively as spina bifida cystica because of the cystlike sac that is associated with them Reference: Netter’s Atlas of Human Embryology, By Cochard, 1st edition Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4 th edition  CONGENITAL ANOMALIES OF THE LOWER NEURAL TUBE DEFECT NEURAL TUBE DEFECT EMBRYOLOGICAL BASIS SPINA BIFIDA WITH - Occurs when the meninges project through a vertebral defect and form a sac filled MENINGOCELE with CSF meningo/o: meninges - Spinal cord and spinal roots are in their normal position, but spinal cord -cele: hernia or pouching abnormalities may be present 1 2 3 SPINA BIFIDA WITH MENINGOCELE 1. Reference: Netter’s Atlas of Human Embryology, By Cochard, 1st edition 2. Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4th edition 3. Reference: Before we are Born- Essentials of Embryology and Birth Defects, By Moore, 8th Edition  CONGENITAL ANOMALIES OF THE LOWER NEURAL TUBE DEFECT NEURAL TUBE DEFECT EMBRYOLOGICAL BASIS SPINA BIFIDA WITH - Occurs when the meninges and spinal cord project through a vertebral defect and are MENINGOMYELOCELE included in the sac meningo/o: meninges -Sac contains meninges, CSF plus spinal neural tissue myel/o: Spinal cord - The spinal neural tissue may be the lower part of the spinal cord or a portion of cauda -cele: hernia or pouching equina 1 2 3 SPINA BIFIDA WITH MENINGOMYELOCELE 1. Reference: Netter’s Atlas of Human Embryology, By Cochard, 1st edition 2. Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4 th edition 3. Reference: Before we are Born- Essentials of Embryology and Birth Defects, By Moore, 8th Edition  CONGENITAL ANOMALIES OF THE LOWER NEURAL TUBE DEFECT NEURAL TUBE DEFECT EMBRYOLOGICAL BASIS RACHISCHISIS - Occurs when the neural folds do not join at the midline and the undifferentiated Greek, rhachis: spine neuroectoderm remains exposed (i.e., neural tube fails to close) schisis: split (Pronunciation: https://www.youtube.com/watch?v=qHcXPuQ9Rdk) RACHISCHISIS TOTALIS - Entire spinal cord remains open RACHISCHISIS PARTIALIS - Spinal cord is partially closed and partially flayed open SPINA BIFIDA WITH RACHISCHISIS 1. Occurs when the posterior neuropore fails to close 2. Creates an open neural tube that lies on the surface of the back 3. Most severe type of spina bifida A: Formation of neural tube B: Rachischisis Reference: Fundamental Neuroscience for Basic and Clinical Applications by Haines, 4 th edition Reference: High-Yield Embryology By Ronald W. Dudek, 2nd Edition  CONGENITAL ANOMALIES OF THE CNS – SELF STUDY (DIAGRAMS) 1 2 Spina bifida with myeloschisis Reference: Before we are Born- Essentials of Embryology and Birth Defects, By Moore, 8th Edition Fetus with a severe case Fetus with anencephaly and IMPORTANT of rachischisis craniorachischisis Myeloschisis: myelo=spinal cord; schisis: split ▪Also called rachischisis 1: Reference: Human Embryology and Developmental Biology, By Carlson, 3rd Edition 2: Reference: Medical Embryology by Langman, 9th Edition CONGENITAL ANOMALIES OF THE CNS – SELF STUDY (DIAGRAMS) C A: Fetus with an occipital meningocele B: Fetus with a frontal encephalocele C: Infant with a myelomeningocele A B Reference: Human Embryology and Developmental Biology, By Carlson, 3rd Edition  Cauda equina: Latin, ‘horse's tail’ Equestrian: Relating to horse riding cauda: tail equine: connected with or relating to horses Posterior view of the lower end of the spinal cord and cauda equina showing their relationship with the lumbar vertebrae, sacrum, and coccyx Reference: Clinical Neuroanatomy By Snell, 7th edition THANK YOU ADDITIONAL RESOURCE: https://www.youtube.com/watch?v=Cu4lQYbOzzY The development of the nervous system