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Neurogenesis (Emília Madarász) Neural stem cells Stem cell: able to divide asymmetrically 1. one of the daughter cells is a copy of the original cell 2. the other daughter cell differs in phenotype – progenitor cell ”they can differentiate into any cell type” We distinguish two types of stem cells: 1. embryonic stem cell (daughter cells can be haploid or diploid) 2. tissue stem cell (daughter cells can only be diploid) – neural stem cells belong here IPSC (Induced Pluripotent Stem Cell): e.g. fibroblast can be reprogrammed to stem cell in vitro goal: cure diseases (Alzheimer, Parkinson, Huntington…) Neurons and glia cells develop from neural stem cells There are neural stem cells in the adult brain too (neurogenic zones): SVZ (SubVentricular Zone), hippocampal formation (SubGranular Zone; SGZ) Neurulation 1 2 Stem cells receive signals that lead to neurulation from neighboring cells (cell-cell signaling), in the nervous system the Notch-Delta system regulates if proliferation or differentiation happens – e.g. AVE1 organizing cells (head – not head region) – e.g. Shh (Sonic hedgehog) morphogen → responsible for shape development Notch – receptor, Delta – ligand of the receptor (on the surface of neural stem cells) they can only bind if two neural stem cells are next to each other Their binding starts a signaling cascade: NICD2 dissociates from the receptor and goes to the nucleus … → induces gene transcription (e.g. Hes gene) → transcription factors that lead to differentiation (e.g. bHLH) Migration of neurons: CNS: with the help of radial glia cells PNS: migration of cells of the neural crest (they migrate to different parts of the body depending on what cell type they differentiate into → regulated by many factors) Axon and dendrite formation are regulated by additional factors growth cone: continuous membrane expansion in the direction where the growth cone is attached (receptors on the surface → determination of growth direction) Apoptosis (in the adult brain there are fewer neurons, but! they form plenty of synapses) Is followed by the formation of synapses (with which cell, how many), networks and their continuous change Synapses can be formed and maintained between synchronously active partners, role of GDP (Giant Depolarizing Potential), ”Fire together, wire together” Anterior Visceral Endoderme Notch IntraCellular Domain