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Spinal Cord Development Spinal Cord Development A. The neural tube caudal to the fourth pair of somites develops into the spinal cord. Neural canal Dorsal nerve rootlet Mesoderm Primordia of spinal ganglion Neural tube Ventral nerve rootlet Spinal Cord Development A. Neural tube 1. Derived from future-neural tube portion of neural ectoderm 2. Forms the central nervous system (brain & spinal cord) B. Dorsal nerve rootlet 1. Derived from neural crest portion of neural ectoderm 2. Forms portion of peripheral nervous system C. Primordia of spinal (dorsal root) ganglion 1. Derived from neural crest portion of neural ectoderm 2. Forms portion of peripheral nervous system D. Ventral nerve rootlet 1. Derived from neural crest portion of neural ectoderm 2. Forms portion of peripheral nervous system Spinal Cord Development A. Composition of Neural Tube Internal limiting membrane Neuroepithelial cells Sclerotomal somitic mesoderm External limiting membrane Spinal Cord Development A. Composition of Neural Tube Internal limiting membrane Internal limiting membrane and external limiting membrane are “true” (extracellular) acellular basement membranes – composed of type-IV collagen, laminin, entactin, nidogen, and cold insoluble fibronectin. Neuroepithelial cells Sclerotomal somitic mesoderm will form bony vertebrae, annulus fibrosis of intervertebral disc (IVD) surrounding forming spinal cord (nucleus pulposus of IVD is formed by notochord), and meninges (dura mater, arachnoid mater, and pia mater) Sclerotomal somitic mesoderm External limiting membrane Spinal Cord Development A. Initially, the wall of the neural tube is composed of a thick, pseudostratified columnar neuroepithelium. Ventricular Zone B. These neuroepithelial cells constitute the ventricular zone (ependymal layer) of the neural tube. C. The ventricular layer gives rise to: 1. All neurons 2. Macroglial cells a. Astrocytes 1. Protoplasmic 2. Fibrous b. Oligodendrocytes 3. Ependymal cells Neuroepithelial cells Spinal Cord Development Marginal zone D. Soon a marginal zone, composed of the outer portions of the neuroepithelial cells, appears. E. This zone gradually becomes the white matter of the spinal cord. F. Axons grow into this area from the spinal cord, spinal ganglia, and brain. Neuroepithelial Cells Spinal Cord Development Intermediate (Mantel) zone G. Some dividing neuroepithelial cells in the ventricular zone differentiate into neuroblasts (primordial neurons). H. The cells form the intermediate (mantel) zone. I. Neuroblasts become neurons as they develop cytoplasmic processes. J. The intermediate (mantel) zone becomes the gray matter of the spinal cord. Neuroepithelial cells Spinal Cord Development K. Neuroepithelial cells in the ventricular zone differentiate into glioblasts. Ventricular zone L. The glioblasts migrate into the marginal and mantel zones from the ventricular zone. M. Some glioblasts differentiate into astroblasts, then astrocytes (protoplasmic and fibrous). N. Some glioblasts differentiate into oligodendroblasts, then oligodendrocytes. Neuroepithelial cells Spinal Cord Development Ventricular zone O. When the neuroepithelial cells finish producing neuroblasts and glioblasts, they differentiate into ependymal cells. P. Ependymal cells form the ependyma, which lines the central canal of the spinal cord. Neuroepithelial cells Neuroepithelial cells Review Slide of neural tube differentiation Neural tube Ependyma Simple cuboidal epithelium covering choroid plexus Neuroblast (Apolar) Glioblast Astroblast Oligodendroblast Neuroblast (Bipolar) Neuroblast (Unipolar) Astrocyte (Protoplasmic) Astrocyte (Fibrous) Oligodendrocyte Neuron Spinal Cord Development – Review Slide Intermediate (mantle) zone (gray matter) Ventricular zone (ependymal layer) Marginal zone (white matter) Developing spinal meninges (dura mater, arachnoid mater, pia mater) Spinal Cord Development Microglial Cells A. Are derived from hematopoietic cells located in the bone marrow B. Formed after week 12 of development C. Migrate to nervous system via the vasculature D. Take up residence in both white matter and gray matter of the CNS E. Are macrophages that function to remove 1. Cell debris 2. Dead and dying cells Spinal Cord Development Myelination of Nerve Fibers A. Myelin sheaths surrounding nerve processes in the CNS 1. begin to form during the late fetal period 2. Continue during the first postnatal year. 3. Formed by oligodendrocytes a. Derivative of neuroepithelial cells B. Myelin sheaths surrounding nerve processes in the PNS 1. Begin about 20 weeks gestation 2. Continue till puberty 3. Formed by Schwann cells a. Derivative of neural crest 4. Motor roots are myelinated before sensory roots Nerve Fiber Coverings Schwann cell nucleus (PNS) or Oligodendrocyte nucleus (CNS) Basement membrane Nerve fiber Unmyelinated axons (5) Each Schwann cell is able to house multiple axons occupying invaginations of its cytoplasm. Myelinated axon (1) Multiple wrapping of Schwann cell plasma membrane (“jellyroll”) around single axon. Myelinated (Motor) Axon Schwann cell Schwann cell nucleus Axon Myelin sheath Node of Ranvier Schwann cell basement membrane Schwann cell process Spinal Cord Development Roof plate A. Proliferation and differentiation of neuroepithelial cells in the developing spinal cord produce thick walls and thin roof plate and floor plate. B. Differential thickening of the lateral walls produces a shallow longitudinal groove on either side, the Sulcus limitans Sulcus limitans Floor plate Spinal Cord Development 1. Signals from sonic hedgehog (Shh) in notochord induces floor plate development. Roof plate BMPs-4 & -7 BMPs-4 & -7 Dorsal 2. BMP-4 & BMP-7 from adjacent ectoderm maintains Pax-3 & Pax-7 expression, dorsally. 3. Sonic hedgehog, produced by the floor plate, suppresses the expression of the dorsal Pax genes (3 & 7) and induces the expression of Pax-6 in the ventral half of the spinal cord. Pax-6 induces formation of motor neurons. Pax-3 Pax-7 Pax-3 Pax-7 Pax-6 Pax-6 Shh Sulcus limitans Ventral Shh Floor plate N Spinal Cord Development Roof plate Alar plate (sensory) C. The Sulcus limitans separates the dorsal part, alar plate, from the ventral part, basal plate. Sulcus limitans Basal plate (motor) D. The alar plate is associated with afferent (sensory) function E. The basal plate is associated with efferent (motor) function. Floor plate Spinal Cord Development F. The alar and basal plates form longitudinal bulges extending through most of the length of the spinal cord. Marginal Zone Alar Plate Sulcus limitans Basal Plate Spinal Cord Development A. Marginal Zone 1. Derivative of neural tube 2. White matter portion of central nervous system B. Alar plate 1. Derivative of neural tube 2. Portion of central nervous system 3. Associated with afferent (sensory) function C. Basal plate 1. Derivative of neural tube 2. Portion of central nervous system 3. Associated with efferent (motor) function D. Sulcus limitans 1. Derivative of neural tube 2. Portion of central nervous system 3. Separates alar plate from basal plate Spinal Cord Development G. Cell bodies in the alar plate form the dorsal (gray) columns that extend the entire length of the spinal cord. These columns are the dorsal horns of the spinal cord. H. Neurons in the dorsal columns constitute afferent nuclei. Afferent nuclei Spinal (dorsal root) ganglion Dorsal columns Dorsal rootlet Afferent sensory neuroblasts in spinal ganglion Dorsal roots of spinal nerve Spinal Cord Development A. Dorsal Columns 1. Derivative of alar plate (neural tube) 2. Portion of central nervous system 3. Neurons in the dorsal columns constitute afferent nuclei B. Dorsal rootlet 1. Derivative of neural crest 2. Portion of peripheral nervous system 3. Composed of Schwann cells and cell processes for sensory neuroblasts in spinal (dorsal root) ganglion C. Afferent sensory neuroblasts in spinal (dorsal root) ganglion 1. Derivative of neural crest 2. Portion of peripheral nervous system 3. Associated with afferent (sensory) function D. Dorsal roots of spinal nerve 1. Derivative of neural crest 2. Portion of peripheral nervous system 3. Cell processes for sensory neuroblasts in spinal (dorsal root) ganglion Spinal Cord Development I. Cell bodies in the basal plates form the ventral and lateral (gray) columns. J. In the spinal cord these are the ventral horn and the lateral horn, respectively. K. Axons of the ventral horn cells grow out of the spinal cord and form the ventral roots of the spinal nerves. Efferent motor neuroblasts Lateral column Ventral rootlet of spinal nerve Ventral roots of spinal nerve Ventral columns Spinal Cord Development A. Ventral Columns 1. Derivative of basal plate (neural tube) 2. Portion of central nervous system 3. Neurons in the dorsal columns constitute efferent nuclei B. Lateral Columns 1. Derivative of basal plate (neural tube) 2. Portion of central nervous system 3. Neurons in the lateral columns constitute efferent nuclei C. Ventral rootlet of spinal nerve 1. Derivative of neural crest 2. Portion of peripheral nervous system 3. Composed of Schwann cells D. Ventral roots of spinal nerve* 1. Derivative of neural tube 2. Portion of central nervous system 3. Cell processes for motor neuroblasts in ventral horn Spinal Cord Development Efferent motor neuroblasts Afferent sensory Sulcus neuroblasts limitans Roof Plate Marginal Zone Dorsal horn Afferent sensory neuroblasts in spinal ganglion Lateral horn Dorsal root of spinal nerve Floor Plate Ventral horn Ventral root of spinal nerve Spinal Cord Development L. As the dorsal marginal zone and alar plates enlarge, the dorsal median septum forms. alar plate dorsal marginal zone Dorsal median septum Spinal Cord Development M. As the basal plates enlarge, they bulge ventrally on each side of the median plane. N. As this occurs, a deep longitudinal groove, the ventral median fissure, develops on the ventral surface of the spinal cord. Basal plate Ventral median septum Spinal Cord Development O. The pseudo-unipolar neurons in the spinal (dorsal root) ganglia are derived from neural crest cells. P. Peripheral processes of spinal ganglion cells pass in the spinal nerves to sensory endings in somatic or visceral structures. Q. The central processes enter the spinal cord and constitute the dorsal roots of the spinal nerves. Axon Dorsal rootlets Spinal (dorsal Pseudoroot) unipolar ganglion neurons Dorsal Roots of spinal nerves Dendrite (conduction towards cell body) Spinal Cord Development R. Axons of the ventral horn cells grow out of the spinal cord and form the ventral roots of the spinal nerves. S. Peripheral processes of ventral horn cells pass in the spinal nerves to motor end plates in somatic or visceral structures. Ventral horn Ventral roots of spinal nerves