Lecture 3 - Development of the Nervous System.pdf

ANAT20040 – Neurosciences Development of the Nervous System - Embryological Basis of Nervous System Structure -  Learning Objectives At the end of this topic, you should: Know the details of development of various parts of the brain and spinal cord; Understand the basic mechan...

ANAT20040 – Neurosciences Development of the Nervous System - Embryological Basis of Nervous System Structure -  Learning Objectives At the end of this topic, you should: Know the details of development of various parts of the brain and spinal cord; Understand the basic mechanism of neural patterning along the cranio-caudal and dorso-ventral axes; Understand disorders of central nervous system embryogenesis  Germ Layers - Review Ectoderm - epidermis structures (e.g. skin, nails, hair), nervous system (neural crest & neural tube) Mesoderm – muscle, connective tissue, blood, blood vessels, skeleton, reproductive & urinary systems Endoderm – epithelium lining digestive & respiratory tracts, digestive organs such as liver & pancreas Early CNS Development All major parts of CNS developed from a simple tube (neural tube)  Neurulation Neurulation – the formation of the primitive nervous system Involves two processes: – Induction of the neural plate, followed by – Formation of the neural tube Neural plate is an ectodermal derivative – ectoderm in midline is induced to form neuroectoderm by the underlying notocord + surrounding tissue Formation of the Neural Tube Neural plate lies above the notochord in the midline dorsally Neural plate rises up into neural folds along its length on each side (neural groove in midline) Cells at the crest of each fold separate to form neural crest cells between the neural plate and surface ectoderm Neural folds fuse together along length to form neural tube Formation of the Neural Tube Neural fold elevation and fusion involves bending at well-defined hinge points 3 hinge points: one MEDIAN & two LATERAL Bending at the median hinge point elevates the folds Bending at the lateral achieves fusion  Neural Fold Fusion Not known exactly what forces drive fusion Cell division is very active in the neuroepithelium Differential growth may determine the lateral hinges and force the tips of the neural folds towards each other Neural Tube Forms CNS CNS Development Newly formed neural tube closes and forms three vesicles in the cranial (anterior) region: – Prosencephalon (forebrain) – Mesencephalon (midbrain) – Rhombencephalon (hindbrain) Extreme cranial end is called the lamina terminalis Caudal to these vesicles are cells which form the spinal cord Subdivisions of Primitive Brain Further paired vesicles grow from the forebrain (telencephalic vesicles) Original part of the forebrain is called the diencephalon Midbrain remains unchanged Hindbrain subdivides into a cranial metencephalon and caudal myelencephalon LATERAL VENTRICLES THIRD VENTRICLE CEREBRAL AQUEDUCT FOURTH VENTRICLE  Derivatives of Primitive Brain Telencephalic vesicles - cerebral hemispheres; enclose lateral ventricles Diencephalon - thalamus; encloses third ventricle Mesencephalon - midbrain; encloses cerebral aqueduct Metencephalon – pons & cerebellum; encloses upper part of fourth ventricle Myelencephalon - medulla oblongata; encloses lower part of fourth ventricle Lateral View of Vesicles Cephalic flexure Pontine flexure Cervical flexure Limited spacing causes the neural tube to bend at three flexures Mechanism of Neural Tube Formation Neural tube closure begins in the cervical region and then proceeds cranially and caudally Temporarily leaves openings called neuropores at either end of the tube (anterior & posterior; communicate with amniotic sac) Primary neurulation (Secondary Neurulation) Only occurs in lower end of spinal cord Here, the neural tube forms from a solid rod of neural tissue which canalises (hollows out) and links up with the rest of the neural tube Closure of Neural Tube Day 25 – Cranial (anterior) neuropore closes Day 25 + 2 – Caudal (posterior) neuropore closes Failure of Closure of Neural Tube Open Neural Tube Defects Failure of caudal part to close is called spina bifida Failure of Closure of Neural Tube Open Neural Tube Defects Failure of cranial part is called anencephaly Total failure is called rachischisis Neural tube defects are relatively common Can be prevented by dietary supplementation (before and during pregnancy) with folic acid Change in Position of Spinal Cord 8 weeks 24 weeks Newborn Adult Cauda equina (‘horse’s tail’) CNS has an Obvious Cranio-Caudal Pattern Neural tube development involves formation of separate regions along its length – Cranially: expands laterally; develops flexures – Caudally: spinal cord – remains a relatively constant width/shape Both give rise to segmental nerves (emerge at discrete points) – regionally specified (involves Hox gene ‘choreographers’) Other patterns of segmentation seen in the bodies of vertebrates (e.g. vertebral column) “The Hox Code” Spinal Cord Development Ependymal (ventricular) layer lines the central canal Mantle layer (intermediate) layer becomes the grey matter of the spinal cord (primarily nerve cell bodies) Marginal layer is formed by neuronal processes and becomes the white matter of the spinal cord Dorsal-Ventral Patterning of the Neural Tube Basal plates produce voluntary (somatic) motor neurones Alar plates produces neurones of the sensory (somatic) pathways Intermediate region (sulcus limitans) produces motor and sensory neurones of the visceral (autonomic) pathways  Establishment of Dorsal-Ventral Pattern Surface ectoderm and roof plate produce growth factors called bone morphogenetic proteins (BMPs) (and Wnts) which induces sensory neurone formation and inhibits motor Notochord and floor plate produce a transcription factor called Shh which induces motor neurone formation and inhibits sensory  Brainstem – Medio-lateral Pattern E.g. Pons/upper medulla Neural tube expands outwards stretching the roof plate out into a broad membrane (ependyma) Brings the sensory nuclei (alar) to lie lateral to the motor regions (basal) Some alar plate neurones migrate ventrally to form special nuclei in the base of the pons and medulla Cerebellum Development Develops from a special part of the metencephalic alar plate called the rhombic lip Neurones from the rhombic lip invade the ependymal roof of the 4th ventricle These form the cerebellar hemispheres and much of the roof of the 4th ventricle  Neural Crest Special part of the dorsal neural groove that is not incorporated into the neural tube on closure Neural crest material migrates away from the tube and populates many distant sites  Fate of Trunk Neural Crest Neural crest migration to skin forms melanocytes Those migrating ventrally form: – Dorsal root ganglia and peripheral sensory neurones – Schwann cells – Autonomic (sympathetic) ganglia – Ganglion cells of gut – Cells of adrenal medulla  Fate of Cranial Neural Crest Cranial neural crest forms some bone of vault of skull and bone around eyes and ears All cranial nerve ganglion cells (PNS) Mesenchyme of pharyngeal arches (bones as above, plus muscles, cartilage)