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Week 4 Notes

Medicine Notes > Organisation of the Body Notes

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-Neuralation involves 4 steps: formation of the neural plate, shaping of the neural plate, bending of the neural plate, closure of the neural groove
-neural plate formation occurs during gastrulation-shaping of the neural plateneural plate narrows in the transverse plane and lengthens in the longitudinal plane
-Key intrinsic neuralation forces: Cell elongation, paraxial microtubules- cells get taller they reduce their diameters. Major factor that narrows neural plate is cell rearrangement, cells move from lateral to medial, rapid cell division where daughter cells are placed along the length of the cell rather than the width Bending of the neural plate: formation of neural folds at the lateral edges of the neural plate- consisting of both neuroepithelium and adjacent surface ectoderm. Neural folds elevate dorsally by rotating around a central pivot point overlying the notochord- median hinge point. Neural plate of the future forebrain is much broader, so there are additional dorsolateral hinge points
-Hinge points involve localised regions where neuroepithelial cells become firmly attached to the notochord (median) or adjacent surface ectoderm (dorsolateral) by deposition of ECM.
-Extrinsic forces created by surface ectoderm and mesoderm, generate forces for folding by changes in cell behaviour, changes in cell shape, position and number Neural groove is formed by the bending of the neural plate-closure of the neural groove- adhesion of the neural folds- followed by rearrangement of cells to form two separate epithelial layers- roof plate of the ectoderm, surface ectoderm
-the neural tube has two pores the cranial and caudal neuropores. As neuralation continues the cranial and caudal neuropores decrease in size and close on DAY 24. Dorso-ventral patterning: surface ectoderm generates dorsal signalling, paraxial mesoderm-lateral signalling and notochord ventral signalling
-Removal of notochords from ventral midline/ transplanted adjacent to the lateral wall- showed the notochord needed for formation of median hinge point and floor plate of neural tube
-SHH is secreted from the notochord- signal that induces the median hinge point and floor plate

-as the floor plate is induced it also secretes SHH, acts as a morphogenventral dorsal concentration gradient within the neural tube- high concentrations induce ventral neurons, lower concentrations induce intermediate neurons, lowerst concentration -dorsal neurons
-Notochord also produces ventral to dorsal concentrations of Chordin, BMP antagonist- Bmp signalling greater at the dorsally as chordin concentration is weak/absent. High level of BMP, Wnt signalling results in induction of neural crest cells of roof plate of neural tube Cranio-caudal patterneing Head: inhibition of Wnt, Bmp signalling- primitive node secretes antagonists Trunk: Wnt, Nodal signlling but inhibition of BMP signalling Tail: Wnt, Nodal signalling and BMP signalling NEURAL TUBE DEFECTS
-Abnormal neuralation: craniorachischisis-entire length of the neural tube opens onto the surface of the head and back, lumbosacral myeloschisis/ spina bifida aperta- only lower most of the spinal cord is opne
-spina bifida occulta: skin covered neural tube defects- location is marked by a tuft of hair- if this occurs in the brain, brain tissue protrudes through the skull
-mild spina bifida occulta- vertebral arches of a single vertebra fail to fuse, underlying neural tube differentiates normally and no protrusion from the vertebral canal
-meningocele- membranes (dura, arachnoid) protrude into the sac but not the spinal meningomyelocele- neural tube and surrounding membranes protrude from the vertebral canal forming a fluid filled sac

Neural crest cells
-interface between epithelial layers- neural crest cells- arise from neural folds and cells undergo epithelial to mesenchymal transformation
-cranial neural crest-development of brain migrate before the closure of the closure of the cranial neural pore, spinal cord the neural crest cells detatch after the neural folds have fused, caudal end neural crest cells detatch after closure of caudal pore
-migration of neural crest cells have been mapped by cell tracing studies in animal models- pathways determined by extracellular matrix molecules which can be permissive/ inhibitory. There are also chemotactic molecules that attract neural crest cells and negative chemotactic molecules

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