Molecular regulation of forebrain development and neural stem/progenitor cells Janne Hakanen Department of Veterinary Biosciences Faculty of Veterinary Medicine University of Helsinki and Developmental Biology Program Institute of Biotechnology and Integrative life science doctoral program (ILS) University of Helsinki Academic dissertation To be presented for public examination with the permission of the Faculty of Veterinary Medicine of the University of Helsinki in the Lecture Hall 7 (Latokartanonkaari 7- B-Building) on 24th of October, 2014, at 12 noon. Supervisor Marjo Salminen, Docent Department of Veterinary Biosciences University of Helsinki Pre-reviewers Juha Partanen, Professor Department of Biosciences University of Helsinki Claudio Rivera, PhD, Research director Neuroscience Center University of Helsinki Opponent Dan Lindholm, Professor Institute of Biomedicine and Minerva Foundation Institute for Medical Research University of Helsinki Custodian Jyrki Kukkonen, Professor Department of Veterinary Biosciences University of Helsinki ISBN 978-951-51-0135-8 (paperback) ISBN 978-951-51-0136-5 (pdf) ISSN 2342-3161 (print) ISSN 2342-317X (online) Table of contents List of original publications Abstract Abbreviations 1. Review of the literature....................................................................................................................1 1. 1 Development of mouse forebrain................................................................................................1 1.1.1 Forebrain germinal zones.......................................................................................................1 1.1.2 Stem/progenitor cells of forebrain germinal zones ................................................................2 1.1.2.1 Self-renewal capacity ........................................................................................................3 1.1.2.2 Interkinetic nuclear migration ...........................................................................................3 1.1.2.3 Symmetric and asymmetric cell divisions.........................................................................4 1.1.3 Forebrain neurogenesis ..........................................................................................................4 1.1.3.1.1 Radial migration....................................................................................................5 1.1.3.1.2 Tangential migration.............................................................................................6 1.1.3.1 Specification of pallium ....................................................................................................6 1.1.3.2 Specification of pallial-subpallial boundary (PSB)...........................................................6 1.1.3.3 Specification of subpallium...............................................................................................7 1.1.3.3.1 Lateral ganglionic eminence (LGE)......................................................................7 1.1.3.3.2 Medial ganglionic eminence (MGE).....................................................................8 1.1.3.3.3 Caudal ganglionic eminence (CGE) .....................................................................8 1.1.3.3.4 Telencephalic stalk................................................................................................9 1.1.4 Forebrain gliogenesis .............................................................................................................9 1.1.4.1 Specification of astrocytes.................................................................................................9 1.1.4.2 Origin and expansion of forebrain oligodendrocytes......................................................10 1.1.4.3 Specification of oligodendrocytes...................................................................................10 1.1.5 Development of adult germinal zones in forebrain..............................................................11 1.1.5.1 Specification of adult germinal zones .............................................................................12 1.1.5.2 Cellular composition of adult SVZ .................................................................................12 1.1.5.3 Adult ependymal cells as neural stem/progenitor cells...................................................12 1.2 Olfactory system ........................................................................................................................13 1.2.1 Development of olfactory system ........................................................................................14 1.2.1.1 Radial glia of olfactory bulb............................................................................................16 1.2.1.2 Development and origin of olfactory bulb projection neurons and LOT........................16 1.2.1.3 Development and origin of olfactory bulb interneurons .................................................17 1.2.1.3.1 Temporal origin of olfactory interneurons..........................................................17 1.2.1.3.2 Lateral ventricle derived interneurons ................................................................18 1.2.1.3.3 RMS derived interneurons ..................................................................................18 1.2.1.3.4 Origin of adult olfactory bulb interneurons ........................................................18 1.2.1.4 Development and origin of olfactory bulb oligodendrocytes..........................................19 1.2.1.4.1 Origin of adult olfactory bulb oligodendrocytes.................................................19 1.2.1.5 Development and origin of olfactory bulb astrocytes and OECs....................................19 1.3 Development of forebrain commissures ....................................................................................20 1.3.1 Fusion of forebrain hemispheres..........................................................................................21 1.3.2 Role of midline cellular populations in development of CC................................................21 1.3.2.1 Glial wedge (GW) ...........................................................................................................22 1.3.2.2 Indusium Griseum (IG) ...................................................................................................22 1.3.2.3 Subcallosal sling (SCS)...................................................................................................22 1.3.3 Callosal axon guidance during formation of CC..................................................................23 1.4 The Netrin family of guidance factors .......................................................................................24 1.4.1 History of Netrins.................................................................................................................24 1.4.2 Netrins in different animal species.......................................................................................24 1.4.3 Molecular structure of Netrins .............................................................................................24 1.4.4 Interactions of Netrins..........................................................................................................25 1.4.5 Interactions and developmental functions of NTN1 in animals...........................................26 1.4.5.1 NTN1 receptor families...................................................................................................26 1.4.5.1.1 DCC and Neogenin .............................................................................................26 1.4.5.1.2 UNC5 family.......................................................................................................27 1.4.5.1.3 Down’s syndrome cell adhesion molecule (DSCAM)........................................27 1.4.5.1.4 Integrins ..............................................................................................................27 1.4.5.2 NTN1 and its receptors in axon guidance .......................................................................28 1.4.5.2.1 NTN1 mediated signaling in axon chemoattraction ...........................................28 1.4.5.2.2 NTN1 mediated signalling in axon chemorepulsion...........................................29 1.4.5.2.3 Switches between NTN1 mediated axon attraction and repulsion .....................30 1.4.5.2.4 NTN1 assisted axon guidance in mouse CNS ....................................................31 1.4.5.3 NTN1 mediated cell migration in CNS...........................................................................32 1.4.5.3.1 NTN1 mediated migration of neurons in mouse CNS........................................32 1.4.5.3.2 NTN1 mediated migration of glial cells in CNS ................................................33 1.4.5.3.3 NTN1 mediated migration of oligodendrocytes in mouse CNS.........................33 1.4.5.4 NTN1 mediated apoptosis through its receptors .............................................................34 1.4.5.5 NTN1 also have a role in organogenesis outside of the nervous system ........................35 1.5 Actin-bundling protein with BAIAP2 homology (ABBA)........................................................35 1.6 Oncogenes affect basic developmental processes of stem/progenitor cells...............................36 1.6.1 Human Papilloma Virus (HPV) 16 E6/E7 oncogenes .........................................................36