DEVELOPMENT of NERVOUS SYSTEM

1. DEVELOPMENT of NERVOUS SYSTEM

2. NEURULATION NEURAL PLATE NEURAL GROOVE NEURAL TUBE NEUROHISTOGENESIS Formation of Neurons and Glial Cells from Neuroepithelium Layers and Plates of the Neural Tube FORMATION OF CNS Development of Forebrain Diencephalon Telencephalon (Brain) Development of Midbrain Development of Hindbrain (Cerebellum) Development of Hindbrain (Medulla Oblogata) Spinal Cord Development DEVELOPMENT OF PNS Neurolemmocytes (Schwan cells) Afferent Neurons Postganglionic Visceral Efferents Neurons Somatic Efferent Neurons and Preganglionic Visceral Efferent Neurons FORMATION OF MENINGES AND VENTRICULER SYSTEM CONTENT

5. Major stages of human CNS development(based on Aicardi 1992)

6. The notochord induces overlaying ectoderm. This ectoderm becomesneuroectodermand form a neuraltube. The following stages of neural tube formation are evident: Neural plate Neural groove Neural tube Neural Crest forming NEURULATION

7. FORMATION OF NEURAL TUBE

8. DERIVATE of NEURAL TUBE and NEURAL CREST CELLS • Neural tube becomes central nervous system (CNS). • The cavity of the tube (neural cavity) becomesthe ventricular system of the brain and the central canal of the spinal cord. • Neural crest cells become those neurons of peripheral nervous system(PNS) that have their cell bodies located in ganglia. • They also becomeneurolemmocytes (Schwann cells) of the PNS. • Additionally, neural crest cellsbecome adrenal medulla cells, melanocytes of skin and a variety of structures in the face.

9. Neuroepithelium gives rise to neurons, glialcells (astrocytesand oligodendrocyte), and ependymal cells. Neuroepithelial cells have processes which contact the inner and outersurfaces of the neural tube. NEUROHISTOGENESIS

11. NEURAL TUBE LAYERS • Ectodermal cells of the early tube develop 3 concentric zones, • 1) germinal (or matrix); Cells near the central canal are called the germinal layer. • Germinal or an internal, columnarependymal layer becomes the ependymal liningandepithelium of choroid plexus, • 2) mantle layer; a middle, denselypacked layer of mantle cells becomes the gray matter of the CNS, • 3) marginal layer; an external marginal layer composed mainly of the processes of cells of the mantle layers becomes the white matter of the CNS.

12. NEURAL CREST DERIVATIVES • LEGEND: • A:Neural Crest • 1a; Bipolar Neuroblast • 1b; Bipolar Neuroblast (Differentiation) • 1c; Unipolar Spinal Ggl. Neuron • 2a; Unipolar Neuroblast • 2b; Multipolar Neuron (SympathicGgl.) • 2c; Medulloblast (Chromaffin Cells) • 3a; Glioblast • 3b; Schwann cell • 3c; Satellite Cell • 4a; Mesenchyme cell • 4b; Leptomeninx cell (Arachnoid & Pia) • 4c; Ectomesenchyme cell • 5a; Melanoblast • 5b; Melanocyte • B: Mantle Zone • C: Marginal Zone • D: Germinal Zone

13. NEUROHISTOGENESIS; MANTLE LAYER DERIVATIVES • LEGEND: • A:Neural Crest • B: Mantle Zone • 7a; ApolarNeuroblast • 7b; Bipolar Neuroblast • 7c; Unipolar Neuroblast • 7d; Mature Neuron • 8a; Glioblast • 8b Protoplasmic Astrocyte • 8c;Fibrillar Astrocyte • 8d;Oligodendrocyte • C: Marginal Zone • D: Germinal Zone

14. NEUROHISTOGENESIS: MARGINAL LAYER DERIVATIVES • Additionally, the CNS containsblood vessels and microglial cells derived from mesoderm. • LEGEND: • A: Neural Crest • B: Mantle Zone • C:Marginal Zone • 9a Mesenchyme cell • 9b Microglia • D: Germinal Zone

15. NEUROHISTOGENESIS: GERMINAL LAYER DERIVATIVES • LEGEND: • A:Neural Crest • B: Mantle Zone • C: Marginal Zone • D:Germinal Zone • 10; Ependymocyte • 11; Choroid Plexus Epithelium • 12; Pinealocyte • 13; Pituicyte

16. Neurons develop from neuroblasts of the neuroepithelium and migrate into the mantle layer. The neuroblast changes into a bipolar cell. Bipolar cell has a primitiveaxon and dendrite. The single dendrite degenerates and is replaced by multiple dendrites forming a multipolar neuroblast. Neurons that fail to make viable contacts are destined to degenerate. NEURON FORMATION

17. NEURAL TUBE HISTOGENESIS • During week 4, the neural groove closes to form a neural tube beginning in the region of the 4th - 6th somites; • Fusion of neural folds proceeds cranially and caudally • Thus Neural tube forms the brain and spinal cord respectively. • Firstly, neural tubes consist of single columnar cell layer. • Then, this layer divides to form a pseudostratifiedneuroepithelium. • So wall of the tube becomes thick and eventually producingneuroblast and glioblast (spongioblast).

18. PATTERN FORMATION OF NEURAL TUBE • Subdivision of the neural tube are specified through pattern formation which take place in TWO directions: • Dorsoventral; generates Longitudinal Areas: • ALAR ( Roof) PLATES; Sensory, • BASAL (Floor) PLATES; Motor • Rostrocaudal; generatesTransverse Zones: NEUROMERES.

19. DORSOVENTRAL PATTERN FOMATION of NEURAL TUBE • Longitidunal groove of midline regions called the sulcus limitans • Sulcus limitans separates the developing gray matter into a dorsal (alar-roof)plate and a ventral (basal-floor) plate.

20. MEDIOLATERAL PATTERN FOMATION of NEURAL TUBE • The basal plate contains efferent neuronsthat sendoutputaxons into the PNS. • The alar plate contains afferentneurons that receiveinput from the PNS.

21. Neuromeresare segmentally arranged transverse bulges along the neural tube, particularly evident in the hindbrain. Each neuromere has alar (dorsal) and basal (ventral) components. Neuromeres gradually fade after day 32 (5 Week; stage 15). ROSROCAUDAL PATTERN FOMATION of NEURAL TUBE

22. Six (6)primary neuromeresappear already at stage 9(18-20 day, week III) when the neural folds are not fused: Prosencephalon (T, D1-D2), Mesomere Four rhombomere (A–D). PRIMARY NEUROMERES Procencephalon LEGEND: T: Telencephalic Neuromere D1-D2: Diencephalic Neuromere M: Mesomere Rh A-D: Rhombomere nch: Notochord mclo:Cloacal Membrane CE: Caudal Eminence

23. Sixteen (16) secondary neuromerescan be recognized from about four week. Six Prosomere (P1-P6) of forebrain A mesomeres (M)of the midbrain, Anisthmicneuromere (I), Eightrhombomeres (Rh1–Rh8). SECONDARY NEUROMERES

24. DERIVATIVES OF THE PROSOMERES • P6: (T) Telencephalicneuromere; Brain Cortex, Medial and Lateral Ganglionic Eminece • P5: Optic Vesicle • P4 (D1) Diencephalic neuromere; medial ganglionic eminence, hypothalamus various part • P3: (D2-P3):The parencephalonrostralis (prospectiveprethalamus) • P2: (D2-P2): The parencephaloncaudalis(prospective thalamus). • P1: (D2-P1): The synencephalon (prospectivepretectum).

25. Even on day19 (Begining of Week III); The neural tube becomesbent by two flexures: (1) the mesencephalicflexure at the midbrain level, already evident beforefusion of the neural folds; (2) the cervical flexure, situatedat the junction between the rhombencephalonand the spinal cord, EARLY DEVELOPMENT OF BRAIN (CNS)

26. The three main divisions of the braincan already be recognized when the neuraltube is not yet closed. These three part: Prosencephalon (Forebrain) Mesencephalon (Midbrain) Rhombencephalon (Hindbrain) EARLY DEVELOPMENT OF BRAIN (CNS)

27. During the FIFTH WEEK (DAY 32 & Stage 15); Reverse, dorsal flexion (pontine flexure) occurs: Begins at the location of the developing pons Mesencephalon enlarges, The prosencephalon rotates ventrally and then posteriorly around this turning point (hinge) during the fourth and fifth weeks until it is folded back under the mesencephalon. The prosencephalon and rhombencephalon each subdivide into two portion. Converting the three primary brain vesicles into five secondary brain vesicles. EARLY DEVELOPMENT OF BRAIN (CNS)

28. EARLY DEVELOPMENT OF BRAIN (CNS) • Future cerebral hemispherescan be recognizedby day 32 (Early Week V). • The forebrain soon divides into an end portion, the telencephalon, and the diencephalon that can be identified because it gives rise to the optic vesicles. • The hindbrain into a rostral (cranial) part develop into the metencephalon, • Metencephalon becomes the cerebellum, the pons and the trigeminal nerve • The hindbrain into a caudal part becomes the medulla oblongata or myelencephalon. • The junction between the hindbrain and midbrain is relatively narrow and is known as the isthmus rhombencephali.

29. FORMATION OF CNS

32. TELENCEPHALONE DEVELOPMENT • LEGEND: • MP:Medial Pallium • DP:Dorsal Pallium • LP:Lateral Pallium • VP:Ventral Pallium • dLGE:Dorsal part of Lateral Ganglionic Eminence • vLGE:Ventral part of Lateral Ganglionic Eminence • MGE:Medial Ganglionic Eminence • A thin roof and lateral part, the pallium, that becomes the future cerebral cortex. • A thick basal (floor) part, the subpallium, that becomes the future basal ganglia

33. DEVELOPMENT OF THE CORTEX • MP:Medial Pallium • DP:Dorsal Pallium • LP:Lateral Pallium • VP:Ventral Pallium • dLGE:Dorsal part of Lateral Ganglionic Eminence • vLGE:Ventral part of Lateral Ganglionic Eminence • MGE:Medial Ganglionic Eminence • AEP/POA: AnteriorEntoPedincular Region / PreOptic Area • The palliumis divided into 4 parts (Based on supposed developmental differences): • A medial palliumor archipallium; Developed hippocampal cortex. • A dorsal palliumor neopallium: Developed neocortex of cerebrum • A lateral palliumor paleopallium: Developed olfactory cortex • Recently, an additional ventral palliumwas added. Ventral pallium is developed by claustroamygdaloid complex • The subpallium consists of three progenitor domains • The Lateral Ganglionic Eminences; generate the striatum (Caudate, Putamen and Accumbens), • The Caudal Ganglionic Eminences; give rise the Amygdala (part of limbic system). • The Medial Ganglionic Eminences (part of diencephalone), generate the globus pallidus.

34. DEVELOPMENT OF THE CORTEX Red: Archeocortex Blue: Paleocortex

36. 4 Month 6 Month 8 Month Neonate Arrow: Central Sulcus

37. During the fetal period, the complex pattern of sulci and gyri arises. On the lateral surface of the brain the sulcus lateralis and the sulcus centralis can be recognized from 4 months (16 week) onwards. FETAL DEVELOPMENT OF THE BRAIN

38. Owing to the development of the prefrontal cortex, the sulcus centralis gradually moves caudalwards. On its medial surface first the parieto-occipital and cingulate sulci appear, Followed by the calcarine and central sulci. The plexus choroideusof the lateral ventricle arises in the lower part of the medial wall of the telencephalic vesicle. FETAL DEVELOPMENT OF THE BRAIN

39. CLASSIFICATION OF THE CORTEX • Based on the differences in lamination the cerebral cortex can be classified into two major groups: • Isocortex (homotypical cortex), the part of the cortex with six layers • Allocortex (heterotypical cortex) with variable number of layers, such as; olfactory cortex and hippocampus.

40. CORTEX CYTOARCHITECTURE • The developing cerebral wall contains several transient embryonic zones: • The ventricular zone is composed of dividing neural progenitor cells; • The subventricular zone (SVZ), which acts early in corticogenesis as a secondary neuronal progenitor compartment and later in development as the major source of glial cells; • The intermediate zone (IZ), through which migrating neurons traverse along radial glial processes;

41. CORTEX CYTOARCHITECTURE • The subplate, thought to be essential in orchestrating thalamocortical connectivity and pioneering corticofugal projections, • The cortical plate, the initial condensation of postmitotic neurons that will become layers II–VI of the mature cortex; • The marginal zone (MZ), the superficial, cell-sparse layer that is important in the establishment of the laminar organization of the cortex.

42. CORTEX CYTOARCHITECTURE • Most pyramidal cells in the cornu Ammonis fields are generated in the first half of pregnancy (24th gestational week). • Granule cells of the dentate gyrus proliferate at a decreasing rate during the second half of pregnancy • After birth but still occur proliferation of granule cells at a low percentage during the first postnatal year.

43. DiencephalicNeuromeres: NeuromereD1 (P4)gives rise to The Medial Ganglionic Eminences (Globus Pallidus), Various part of Hypothalamus The diencephalicneuromereD2 (ProsomeresP1-3) can be further subdivided into The synencephalon (P1) (prospectivepretectum), The parencephaloncaudalis(P2) (prospective thalamus), The parencephalonrostralis (P3). (prospective prethalamus). DIENCEPHALON DEVELOPMENT

45. DIENCEPHALON DEVELOPMENT • The alar component of the synencephalon forms the pretectum, • The caudal parencephalon (alar component)forms the dorsal thalamus and epithalamus, • The rostral parencephalon(alar component)forms the ventral thalamus. • The basal components jointly form the prerubraltegmentum.

46. THALAMUS DEVELOPMENT • ET: Epithalamus; • DT: Dorsal Thalamus • VT: Ventral Thalamus • TE: Thalamic Eminence • HT: Hypothalamus • Str: Striatum • DG: Dentate Gyrus • Hp: Hippocampus • LV: Lateral Ventricle • VP: Ventral Pallium • The thalamus acts primarily as the relay center for the cerebral cortex. • It receives all the information (sensory and other) projecting to the cortex from subcortical structures. • All information processes thalamus. • If it can necessary, appropriate cortical area'scommunicates.. • The Thalamus includes: • The sense of sight (vision) is handled by the lateral geniculate body • The sense of hearing by the medial geniculate body.

47. HYPOTHALAMUS DEVELOPMENT • The hypothalamus regulates the endocrine activity of the pituitary as well as many autonomic responses. • It participates in the limbic system, which controls emotion and coordinates emotional state with the appropriate visceral responses. • The hypothalamus also controls the level of arousal of the brain (sleep and waking). • The small epithalamus gives rise to a few miscellaneousstructures.

48. MESENCEPHALON DEVELOPMENT • The Mesencephalon is primarily a relay (communicate) center. • Midbrain also contain cranial nerve nuclei, visual and auditory centers and other structures. • Much of the mesencephalon is composed of white matter, • Principally the massive tracts connectthe forebrain with the hindbrain and spinal cord.

49. MESENCEPHALON DEVELOPMENTFOUR CRANIAL NERVE NUCLEI • The midbrain also contains a number of importantneuronal centers, including four cranial nerve nuclei. • Themotor nuclei of the oculomotor(III) • Thegeneralvisceral efferent (Edinger-Westphal)nucleus • Themotor nuclei of the trochlear (IV) nuclei • A portion of the sensorynucleus of the trigeminal nerve (V) called themesencephalic trigeminal nucleus • Thetrochlear and mesencephalic trigeminalnuclei originate in the metencephalon and are secondarilydisplaced into the mesencephalon.

50. Only the two serving theoculomotor nerve arise from mesencephalicneuroblast; Thesomaticmotor oculomotor nucleus controlsthe movements of all but the superior oblique andlateral rectus extrinsic ocular muscles, TheEdinger-Westphal nucleussupplies parasympathetic pathways to thepupillary constrictor and theciliarymuscles of theeyeglobe. MESENCEPHALON DEVELOPMENTFOUR CRANIAL NERVE NUCLEI