CMM/BIO4350

Tues March 20, 2012

Diane Lagace, PhD

Assistant ProfessorDepartment of Cellular and Molecular Medicine (CMM)

Neuroscience ProgramRGH, Room 3510G, University of Ottawa,

dlagace@uottawa.ca

7 Lectures1. 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)• Regeneration of the Nervous System

From lecture notes only; not in text book• Chemical Controls of Brain and Behavior

Chapter 15: Hypothalamus, ANS, Neurotransmitter Systems (p482-504)1. Motivation and Homeostasis

Chapter 16: Feeding Regulation Short and Long-Term and Why We Eat (p510-527)• Sex and the Brain

Chapter 17 (p534-561)

What Do I Need to Know?

Text book

Notes

Both

Outline Lecture #1

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 HypoblastChick Embryo

http://www.usm.maine.edu/bio/courses/bio205/bio205_05__development_1.html

http://www.gastrulation.org/Movie15_1.avi

http://www.usm.maine.edu/bio/courses/bio205/bio205_05__development_1.html

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 discDynamic movement of cells to form three germ layers:

Ectoderm, Mesoderm, and Endoderm

1 Primitive groove2 Primitive pit3 Primitive node4 Oropharyngeal membrane5 Cardial plate6 Sectional edge of amniotic membrane7 Mesoderm8 Endoderm9Future cloacal membrane1+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

Anteriorneuralpore

Posteriorneuralpore

failure to close = anencephaly

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

Crane and Trainor 2007

+ connective tissue around face and head

Peripheral Nervous System (PNS)

NP, neural precursor;MP, melanocyte precursor; NGP, neuron/glia precursor; CP, cardiac precursor.

Neural crest specification: migrating into genomicsLaura S. Gammill & Marianne Bronner-FraserNature 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/unit-nervous/nerv_htms/nerv009.htm#

mesencephalon

metencephalon

myelencephalon

6 weeks4 weeks

Five-vesicle stage

p 185

Holoprosencephaly (HPE) is a congenital anomaly in which there is incomplete development of the brain.

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/holoprosencephaly/holoprosencephaly.htm

Lobar HPE Alobar HPE

http://www.ncbi.nlm.nih.gov/books/NBK1530/

Differentiation of Forebrain

The neurons of the telencephalon wall proliferate to form 3 distinct regions1)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 axonsCorpus 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

– 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

Midbrain Structure Function

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

p 188-189http://www.youtube.com/watch?v=9BaWBGRVxp8&feature=related

Copyright © 2009 Allyn & Bacon

TELENCEPHALON GIVES RISE TO MAJORITY OF STRUCTURES

Differentiation of Spinal Cord

p 190-191

Movie: http://www.youtube.com/watch?v=LwuV5JbgCNk

Putting the Pieces Together

p 192

Summary

1. GastrulationFormation 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)