Development of CNS PDF

Development of spinal cord & NTD Dr.Yasir Elhassan Associate professor Clinical Anatomist Modified by Prof Ghada Wassif Prof.: Ghada Wassif Embryonic disc bilaminar Epiblast Hypo...

Development of spinal cord & NTD Dr.Yasir Elhassan Associate professor Clinical Anatomist Modified by Prof Ghada Wassif Prof.: Ghada Wassif Embryonic disc bilaminar Epiblast Hypoblast Prof Ghada Wassif Gastrulation: 3rd week 1- Formation of primitive streak (linear band of thickened epiblast cells that first appears at the caudal end of the embryo and grows cranially. At the cranial end its cells proliferate to form the primitive knot (primitive node) Primitive streak Prof Ghada Wassif Gastrulation: 3rd week 1- Formation of primitive streak (linear band of thickened epiblast cells that first appears at the caudal end of the embryo and grows cranially 2- Formation of trilaminar embryonic disc 3- Development of notochord Ectoderm Intraembryonic Mesoderm Definite Endoderm Prof Ghada Wassif  Definitive notochord is a rod like structure starts in the middle of the embryo, and proceeds in both cranial and caudal directions. It arises from axial mesoderm at about 16 days and is completely formed by the beginning of the fourth week. It defines the embryonic midline. Prof Ghada Wassif  Of Notochord It defines the longitudinal axis of the embryo, determines the orientation of the vertebral column, and persists as the nucleus pulposus of the intervertebral discs. Prof Ghada Wassif The mesoderm moves to the midline until it covers the notochord, it proliferates to form the paraxial mesoderm. On each side, the mesoderm remains thin and is known as the lateral plate. The intermediate mesoderm lies between the paraxial mesoderm and the lateral plate Prof Ghada Wassif The Nervous Syst. Begins to develop during the 3rd wk. Derived from ectoderm (neuroectoderm) Except the microglia & dura mater which are mesodermal. Ectoderm Mesoderm Embryonic disc Endoderm Prof Ghada Wassif  NS-----Formation of the Neural Tube (Neurulation) In the 3rd wk, the embryo is in the form of trilaminar, pear-shaped disc. The 3 layers are: Ectoderm (epiblast) dorsally, Endoderm ventrally and Mesoderm in between. Head Ectoderm Mesoderm Endoderm Prof Ghada Wassif  The ectodermal layer is induced to form the neural plate by the underlying notochord & paraxial mesoderm Neural plate The edges of the neural plate called Neural Folds. The neural folds approximate till they finally fuse together in the midline Prof Ghada Wassif forming the Neural tube Neural plate forms at the cranial ends of the embryo & grows in a cranio-caudal direction Prof Ghada Wassif At the same time the neural crest is disconnect from the epidermis. Prof Ghada Wassif  The ectodermal layer is induced to form the neural plate by the underlying notochord & paraxial mesoderm The ectoderm is thickened in a median area on the dorsal aspect of the embryonic disc to form neural plate. The edges of the neural plate called Neural Folds. The plate itself invaginates forming the Neural groove. The folds gradually raised is referred to as neural crest. The neural folds approximate till they finally fuse together in the midline forming the Neural tube. At the same time the neural crest Prof is Ghada disconnect Wassif from the epidermis.  The neural tube before completely closed it is divided into a large cranial part and a caudal tubular part which later on gives rise to the brain and spinal cord Paraxial mesoderm form the axial skeleton ( vertebral & ribs) During neurulation, ectoderm differentiates into two parts. The first is the surface ectoderm, which gives rise to tissues on the outer surface of the body like epidermis, hair, and nails. The second is the neuroectoderm, which forms the nervous system of the embryo. Development of the skull: Lateral plate mesoderm found in the neck region, paraxial mesoderm and neural crest cells Neural groove Neural crest Neural tube Neural Plate Surface Neural crest Neural fold ectoderm Notochord Paraxial mesoderm Notochord Yolk sac Prof Ghada Wassif Cross section of trilaminar embryonic disc Derivatives of the neural crest: 1- Nervous tissue - Leptomeninges (pia & arachnoid) - Schwann cells 2- Sensory ganglia -Spinal (DRG) -Autonomic g (sympathetic and parasympathetic) 3-Endocrine tissue -Adreno-medullary cells -Calcitonin C cells of thyroid g. -Carotid body 4-Connective tissue -Bone and cartilage of facial skeleton 5-Muscles tissue -Ciliary muscles 6-Pigment -Melanocytes Prof Ghada Wassif Neuropores Neural groove begins fusion cervically and proceeds both cranially and caudally. The cranial & caudal ends of the neural groove remain patent forming the ant. & post. neuropores which close later (ant. on 25th day & post on 27th day) Prof Ghada Wassif  Closure of Neuropores The rostral neuropore closes on the 25th day the caudal neuropore closes on the 27th day Rostral neuropore closing Neural groove Forebrain prominence Heart prominence Rostral neuropore Neural tube Yolk stalk Somites Somites Caudal neuropore Connecting stalk Prof Ghada Wassif Caudal Amnion neuropore  Development of brain Brain develops from cranial part of neural tube Midbrain flexure Midbrain Hindbrain Optic vesicle Cervical flexure Dorsal root ganglion Forebrain Prof Ghada Wassif Prof Ghada Wassif  Prosencephalon Lateral V. 3rd V. Cerebral Mesencephalon aqueduct Rhombencephalon Brain stem 4th V. Prof Ghada Wassif V.: ventricles Brain is derived from the cranial part of the neural tube. Prof Ghada Wassif Prof Ghada Wassif  Development of spinal cord Spinal cord develops from narrow caudal part of neural tube Midbrain flexure Midbrain Hindbrain Optic vesicle Cervical flexure Dorsal root ganglion Forebrain Prof Ghada Wassif  Spinal cord development Neural tube is lined by thick layer of neuroepithelium which forms the ventricular zone Marginal zone forms superficial to ventricular zone Primitive neuroepithelial cells in the ventricular zone multiply and newly formed cells move out to form the intermediate zone ( mantle layer) between the ventricular zone and the marginal zone. Cells in the intermediate zone differentiate into neuroblasts which form neurons Ventricular zone Marginal zone Intermediate zone Prof Ghada Wassif  3 zones in the wall of the neural tube Ventricular zone Ependymal devoid of cell bodies Prof Ghada Wassif  Alar and basal plates The mantle zone thickens in 4 regions in the wall of the neural tube As a result the lumen becomes rhomboidal & shows: Roof plate 1. A pair of alarplates dorsally 2. A pair of basal plates ventrally 3. A pair of sulcus limitans in the lateral walls 4. A roof plate & 5. A floor plate Floor plate Prof Ghada Wassif Cross section of neural tube  Grey and White matter of spinal cord Marginal zone forms the white matter Mantle zone forms the grey matter Ependymal zone forms the ependymal lining of the central canal Cavity of neural tube forms the central canal Part of mantle lay.dorsal to sulcus limitans called alar plate Part of mantle lay. ventral to sulcus limitans called basal plate Alar lamina forms the dorsal grey horn- sensory Basal lamina forms the ventral & lateral grey horns- motor Neural Tube Defect ( NTD) Causes of NTD Prof Ghada Wassif 1. Genetic 2. Folate deficiency (Folic acid is a B vitamin). Folate plays an important role in forming red blood cells and maintaining brain health NTD occurs 26 days post-fertilization – when many woman don’t know they are pregnant. Ingestion of preconception F. Acid is not easy (less than 50% of pregnancies are planned). Folic Acid is not protective unless ingested in preconception period. Prof Ghada Wassif 3.Teratogens: are substances that cause congenital disorders in a developing embryo or fetus ▪ Hyperthermia in early pregnancy ▪ Nutr. Deficiencies ▪ Hypervitaminosis A & deficient or inadequate maternal vitamin B12 ▪ Drugs: 1- Epilepsy medication a-Valproic acid (sodium valproate e.g: Depakine), altered folate metabolism b- Carbamazepine = folate antagonists 2- Sulfonamides (competitively inhibit enzymes that function in synthesis of folic acid) 3- Antihistaminics (chlorpheniramine) Prof Ghada Wassif  Neural Tube Defect ( NTD) 1-Primary defect: Failure of neural folds to fuse in midline and form neural tube Failure of neuropore to close. 2- Maldevelopment of mesoderm (forms skeletal (vertebrae &ribs) and muscular (back Ms) structures that cover neural structures). Prof Ghada Wassif  Clinical notes 1. Anencephaly: One of the most common NTDs Absence of calvarium, posterior bone elements (skull) and deficiency in brain (prosencephalus) N. meninges. Occurs when the neural tube fails to close at the base of the skull (Failure of rostral neuropore to close) No survival possible. D:Alfa-fetoprotein in maternal serum & amniotic fluid increased NB:The bones of the skull, developsProf from neural Ghada Wassif crest cells and paraxial and lateral plate mesoderm.  Clinical notes 2. Sacral spinal sinus: A skin dimple in the mid sacral region. They result from focal failure of dysjunction between the cutaneous ectoderm and neuroectoderm during the third to eight week of gestation Cause abnormal ectodermal adhesion of the neural tube to the dermis. 3. Spina bifida: due to failure of fusion of the two Prof Ghada Wassif vertebral arches, more common in the lumbosacral region. Anencephaly with spina bifida Prof Ghada Wassif  Types of spina bifida Occulta With meningocele No bulge over the bony defect A bulge is seen over the defect A skin dimple contains meninges & CSF in the Or tuft of hairs may be present subarachnoid space Over unfused vertebral arches No neurological symptoms Unfused vertebral arch Dura mater Tuft of hair Skin Subarachnoid space (containing cerebrospinal fluid) Spinal cord Back muscles Vertebra Prof Ghada Wassif  A. Spina bifida occulta No bulge over the bony defect A skin dimple Or tuft of hairs may be present Over unfused vertebral arches No neurological symptoms Prof Ghada Wassif  Types of spina bifida With meningomyelocele With myeloschisis A bulge is seen over the defect Over the bony defect open Contains meninges, cord & nerves spinal cord is seen as a mass of neural tissue Membranous sac Dura mater Open spinal cord Displaced spinal cord Skin Roots of spinal nerve C D Subarachnoid space Spinal ganglion Prof Ghada Wassif Spina bifida with Spina bifida with meningomyelocele myeloschisis Prof Ghada Wassif  Resources This lecture on web Sadler, T (2004)Langman’s Medical Embryology (9th Edition)Lippencott Larsen, W (1997) Human Embryology (2nd Edition) Churchill Livingstone – fairly accurate but really only for reference Prof Ghada Wassif