CMM/BIO4350 Tues March 20, 2012 Diane Lagace, PhD Assistant Professor Department of Cellular and Molecular Medicine (CMM) Neuroscience Program RGH, Room 3510G, University of Ottawa, dlagace@uottawa.ca 7 Lectures 1. Embryonic Development 101 Chapter 7: Understanding CNS structure through development (p178-201) 2. Gross Neuroantaomy Chapter 7: Gross Organization of Mammalian Nervous System (p168-176) Chapter 7 Appendix: Illustrated Guide to Human Neuroanatomy (p206-248) 3. The Genesis of the Neuron (Neurogenesis) and Neuronal Connections Chapter 23: The Genesis of Neuron, Connections and Elimination of Cells and Synapses (p690-707) 4. Regeneration of the Nervous System From lecture notes only; not in text book 5. Chemical Controls of Brain and Behavior Chapter 15: Hypothalamus, ANS, Neurotransmitter Systems (p482-504) 6. Motivation and Homeostasis Chapter 16: Feeding Regulation Short and Long-Term and Why We Eat (p510-527) 7. Sex and the Brain Chapter 17 (p534-561) What Do I Need to Know? Text book Notes Both Outline Lecture #1 1. Gastrulation Formation of 3 germ layers (not in text book) 2. Neurulation: Formation of neural tube (p. 180-183) 3. Differentiation and Formation of the Major Subdivision of the Brain Forebrain, Midbrain, Hindbrain (p. 182-190) 4. Differentiation of the Spinal Cord (p. 190-191) 5. The Cerebral Cortex (p 195-199) Thursday How Does the Brain and Spinal Cord Develop? Video http://www.youtube.com/watch ?v=UgT5rUQ9EmQ Human Development Inner Cell Mass Forms 2 Layer: Epiblast and Hypoblast Chick Embryo http://www.gastrulation.org/Movie15_1.avi http://www.usm.maine.edu/bio/courses/bio205/bio20 ment_1.html http://www.usm.maine.edu/bio/courses/bio205/bio205_05__de ml Images of human embryos during gastrulation,13 - 19 days post ovulation http://biology.kenyon.edu/courses/biol114/Chap14/Chapter_14.html#Neurulation http://stemcells.nih.gov/info/scireport/appendixa.asp Trilaminar germ disc Dynamic movement of cells to form three germ layers: Ectoderm, Mesoderm, and Endoderm 1 Primitive groove 2 Primitive pit 3 Primitive node 4 Oropharyngeal membrane 5 Cardial plate 6 Sectional edge of amniotic membrane 7 Mesoderm 8 Endoderm 9Future cloacal membrane 1+2+3 primitive streak http://www.embryology.ch/anglais/hdisqueembry/triderm01.html#formligneprim A cut through the embryo illustrates the three germ layers: ectoderm (formerly referred to as epiblast), mesoderm, and endoderm. Mouse E7, Human ~17days http://biology.kenyon.edu/courses/biol114/Chap14/Chapter_14.html Ectoderm (OUTER LAYER) Ectoderm forms tissues associated with outer layers: skin, hair, sweat glands, epithelium. The brain and nervous system develop from the ectoderm. Mesoderm (MIDDLE LAYER) The mesoderm forms structures associated with movement and support (skeleton and muscles): body muscles, cartilage, bone, blood, and all other connective tissues. Reproductive system organs and kidneys form from mesoderm. Endoderm (INNER LAYER) The endoderm forms tissues and organs associated with the internal organs (digestive and respiratory systems). Many endocrine structures, such as the thyroid and parathyroid glands, are formed by the endoderm. The liver, pancreas, and gall bladder arise from endoderm. p 180-181 The CNS forms from the walls of a fluid-filled neural tube – The inside of the tube becomes ventricular system – The neural tube • Endoderm, mesoderm, ectoderm • Neural plate neural groove • Fusion of neural folds • Neural tube (forms Central Nervous System (CNS) neurons) :NEURULATION • Neural crest (forms Peripheral Nervous System (PNS) neurons) • Somites (form vertebrae of spinal column and related muscle) p181 p181 Primary neurulation p181 Neural Tube Related Birth Defects Anterior neural pore failure to close = anencephaly Posterior neural pore failure to close = spina bifida p 183 • Neural crest becomes peripheral nervous system (PNS) • Neural tube becomes central nervous system (CNS) • Somites become spinal vertebrae. Somites p 181 Neural Crest Stem Cells Peripheral Nervous System (PNS) + connective tissue around face and head NP, neural precursor; MP, melanocyte precursor; NGP, neuron/glia precursor; CP, cardiac precursor. Crane and Trainor 2007 Neural crest specification: migrating into genomics Laura S. Gammill & Marianne Bronner-Fraser Nature Reviews Neuroscience 4, 795-805 (October 2003) FROM THE NEURAL TUBE TO THE BRAIN Closure of neural tube have around 125,000 cells. At birth, the human brain contains around 100 billion neurons We can infer from this information that new neurons are being generated at the rate of about 250,000 per minute during the nine months of gestation. (Cowan, 1979) http://faculty.washington.edu/chudler/dev.html Three-vesicle stage (Week 4) p 182-184 A cut through the recently closed cranial neural tube illustrates the forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon). E10 mouse, human ~5 week http://www.med.unc.edu/embryo_images/unitnervous/nerv_htms/nerv009.htm# Five-vesicle stage mesencephalon metencephalon myelencephalon 4 weeks 6 weeks p 185 Holoprosencephaly (HPE) is a congenital anomaly in which there is incomplete development of the brain. Alobar HPE Lobar HPE http://www.ncbi.nlm.nih.gov/books/NBK1530/ In utero, the developing forebrain (prosencephalon) fails to divide into two separate hemispheres and ventricles. Specifically, there is incomplete cleavage into right and left hemispheres; into the telencephalon and diencephalons; and into the olfactory and optic bulbs and tracts. Based on the level of cleavage, holoprosencephaly is classified into 4 subtypes: Alobar, Semilobar, Lobar and MIHV. http://www.ninds.nih.gov/disorders/holoprosencep /holoprosencephaly.htm Differentiation of Forebrain The neurons of the telencephalon wall proliferate to form 3 distinct regions 1)cerebral cortex 2) the basal telencephalon, and 3) the olfactory bulb The diencephalon differentiates into the thalamus and the hypothalamus GREY MATTER: Collection of neuronal cell bodies in CNS p 180, 184-5 Formation of Ventricles and White Matter Ventricles: Fluid filed spaces: lateral and third ventricle WHITE MATTER: Collection of CNS axons Corpus Callosum: axonal bridge link cortical neurons from 2 hemispheres p 180, 184-5 Differentiation of Midbrain Function as passageway for the bundles of fibers that connect the cortex to the spinal cord (sensory and motor) p 187-188 Midbrain Structure Function – Contains axons descending from cortex to brain stem and spinal cord • e.g., Corticospinal tract – Information conduit from spinal cord to forebrain and vice versa, sensory systems, control of movements – Tectum Superior colliculus (receives sensory info from eye), inferior colliculus (receives sensory info from ear) – Tegmentum • Substantia nigra (black substance) and red nucleus – control voluntary movement p 187-188 Differentiation of Hindbrain (Rostral / Caudal) Rostral portion of the hindbrain differentiates into two major structures: the cerebellum and the pons. p 188-189 Hindbrain Structure Function – Cerebellum: Movement control – Pons: Switchboard connecting cerebral cortex to cerebellum – Cochlear Nuclei: Project axons to different structures (e.g., inferior colliculus) – Decussation: Crossing of axons from one side to the other http://www.youtube.com/watch?v=9BaWBGRVxp8&feature=related p 188-189 TELENCEPHALON GIVES RISE TO MAJORITY OF STRUCTURES Copyright © 2009 Allyn & Bacon Differentiation of Spinal Cord Movie: http://www.youtube.com/watch?v=LwuV5JbgCNk p 190-191 Putting the Pieces Together p 192 Summary 1. Gastrulation Formation of 3 germ layers 2. Neurulation: Formation of neural tube 3. Differentiation and Formation of the Major Subdivision of the Brain (Forebrain, Midbrain, Hindbrain) and Spinal Cord Question Last Year Fill in the blanks (answers in italics) (½ mark for each blank) During the process of ___neurulation____ the neural tube is formed, which becomes the __brain__ and __spinal cord____ in the adult . (1 ½ marks). Failure of the developing forebrain (prosencephalon) to divide into two separate hemispheres and ventricles results in a congenital anomaly called __holoprosencephaly (HPE)_(1/2 mark) At the 3 vesicle stage of development of the embryo the prosencephalon is also called the forbrain. The prosencephalon gives rise to the __telencephalon____ and ___ diencephalon__ at the 5 vesicle stage of development. (1 mark)