Neurogenesis Past Paper PDF

BIO344 HS2024 Neurogenesis Esther Stoeckli Proliferation Differentiation Cell migration Axonal pathfinding Connectivity Synapse formation Circuit formation Maturation Cell death Prun...

BIO344 HS2024 Neurogenesis Esther Stoeckli Proliferation Differentiation Cell migration Axonal pathfinding Connectivity Synapse formation Circuit formation Maturation Cell death Pruning Proliferation 1. Gastrulation frog produces the three germ layers: ectoderm mesoderm endoderm chicken Cells moving through the blastopore lip trigger axis formation Transplantation experiments by Hilde Mangold and Hans Spemann resulted in the induction of a second body axis and the discovery of the Organizer Node Hensen‘s Node Sanes, Reh, Harris, 2006 Dissection of pregastrula animal cap cells reveals neuronal development as the default pathway BMP = bone morphogenetic protein Sanes, Harris, Reh, 2012  Timing is important during development ! Sanes, Reh, Harris, 2012 Neural development is the default pathway 1. Gastrulation 2. Neurulation forms the neural tube Embryonic development can easily be studied in chicken embryos due to their accessibility in the egg Wolpert, 2002 Gastrulation in the chicken embryo Wolpert, 2002 Neural development proceeds along a rostro-caudal gradient Wolpert, 2002 During neurulation the neural ectoderm / neural plate forms a furrow and finally closes to form the neural tube nach Wolpert, 2003  2. Neurulation The neural tube is the orgin of the CNS and neural crest cells, which will give rise to the PNS Gilbert, 2003 Martik & Bronner, 2017 Now we have a neural tube, so what ? Proliferation Asymmetric cell division Numb chromosomes Sanes, Reh, Harris, 2012 Cells proliferate in the ventricular zone of the neural tube Time matters during neurogenesis Sanes, Harris, Reh, 2012 Neuroepithelial cells migrate along the apical-basal axis during the cell cycle (interkinetic nuclear migration) Wolpert, 2002 Asymmetric cell division gives rise to different daughter cells Götz and Huttner SNAREs decide on symmectric versus asymmetric cell division Götz and Huttner The overall length of the progenitor cell cycle increases during embryogenesis Sanes, Reh, Harris, 2006 The cell-cycle length hypothesis explains the progression from symmetric to asymmetric cell division Götz and Huttner, 2005 Cell proliferation occurs in specialized areas of the nervous system: - ventricular zone - subventricular zone - external germinal/granule cell layer The cerebellum has two main zones where neurons are born VZ ventricular zone EGL external granule cell layer How do cells adopt a specific fate ? Cell differentiation How to make neural precursors Lateral Inhibition  Lateral Inhibition defines the number of neural precursor cells Wolpert, 2002  Activation of Notch signaling prevents commitment of cells through activation of respective gene expression pattern γ-secretase HES proneural genes Wolpert, 2002 Notch activity shuts down proneural genes with stage- or context-dependent outcome Bertrand et al., 2002 Progenitor cells in the retina give rise to different cell types depending on time G Ganglion cells A Amacrine cells H Horizontal cells B Bipolar cells C Cones R Rods M Müller glia cells Sanes, Harris, Reh 2012 Oligodendrocytes and motoneurons are derived from the same progenitor pool Sances, Harris, Reh 2012 Patterning the nervous system  How do cells become different from each other ? The French Flag Model How do cells become different from each other ? The French Flag Model Neurulation gives rise to a polarized neural tube Martik & Bronner, 2017  BMP and SHH polarize the dorso-ventral axis of the neural tube Sanes, Reh, Harris, 2006 Shh ventralizes the spinal cord Sanes, Harris, Reh 2012 The concentration of Shh determines the cell type in the ventral spinal cord Shh represses class I homeodomain genes but induces class II genes Wolpert, 2002 Mutual repression produces sharp boundaries Shh and BMP gradients pattern the dorso-ventral axis of the neural tube Sanes, Harris, Reh 2012 Neurons along the dorso-ventral axis of the neural tube are characterized by specific patterns of transcription factor expression Sanes, Harris, Reh 2012  The Notochord Chorda dorsalis Sanes, Reh, Harris, 2006 A transient mesodermal structure required for the patterning of the neural tube. The notochord is required..... Sanes, Reh, Harris, 2006...and sufficient to induce the floor plate Sanes, Reh, Harris, 2006 Patterning the longitudinal axis The brain contains two organizers that pattern the brain along the AP axis MHB Mid-Hindbrain- Boundary ZLI Zona Limitans Intrathalamica Model for boundary formation Hox genes specify compartments along the anterior-posterior axis Hox genes are conserved throughout evolution The longitudinal axis is organized by Hox gene expression patterns Sanes, Harris, Reh 2012 Rhombomere identity is determined by the Hox code Sanes, Harris, Reh 2012 Cranial nerves and their primary function I Olfactory nerve sensory sense of smell II Optic nerve sensory vision III Oculomotor nerve motor eye movement, papillary constriction, muscles of eye lid IV Trochlear nerve motor eye movement V Trigeminal nerve sensory and motor sensation from face, mouth, mastication VI Abducens nerve motor eye movement VII Facial nerve sensory and motor muscles controlling facial expression, taste from anterior tongue VIII Vestibulocochlear sensory hearing, sense of balance nerve IX Glossopharyngeal nerve sensory and motor sensation from pharynx, taste from posterior tongue X Vagus nerve sensory and motor autonomic function of gut, sensation from pharynx, muscles of vocal cords, swallowing XI Spinal accessory nerve motor shoulder and neck muscles XII Hypoglossal nerve motor movements of the tongue Compartments and their boundaries in vertebrate brain development C. Kiecker and A. Lumsden Nat.Rev.Neurosci. 6(2005)553-564 additional (non-mandatory) reading Summary Basic patterning mechanisms are conserved between vertebrates and invertebrates Organizers secrete morphogens which induce specific gene expression patterns in responsive cells Responsive cells differentiate to distinct cell types according to the morphogen concentrations found at their location Boundaries are formed by a combination of mutual repression and cell sorting Timing is important in development!