Lecture 8 Flashcards
How do we make a brain
Sperm and ovum fertilisation (single cell) develops into one
1x10^11 neurons in brain
2.5x10^15 connections
40 known transmitters
Overview of neural development process
Sperm and egg fertilisation forms a zygote
Zygote forms blastocysts
Blastocysts form gastrula
gastrula forms a fetus -> human
Human morula formation
Morulas are formed from cell division of the zygote over a 4 day period
Contained in the zona pellucida so not growth in size
Resemble a mulberry
In latter compaction stage, individual cells become less distinct
Morula to blastocyst
On day 4 (morula), cells secrete fluid and outermost cells become tightly bound together in the process of compaction. Zona pellucida disappears
On day 5, inner cell mass or embryoblast forms embryo and source of pluripotent embryonic stem cells give rise to adult structures, including the nervous system. The trophoblast later forms the placenta
Gastrulation forms primary germ layers
Epiblast cells form inner cell mass converge at midline and ingress at primitive streak.
Two layers (epiblast and hypoblast) are transformed into three layers (mesoderm, ectoderm, endoderm).
Chick Embryo Gastrulation
What do the three germ layers form
Ecotderm: Skin, nails, hair, eye lens, ear, nose, sinuses, mouth, anus, tooth enamel, pituitary gland, mammary glands and nervous system
Mesoderm: Muscles, bones, lymphatic tissue, blood cells, heart, lungs and reproductive system
Endoderm: Lung lining, tongue, tonsils, urethra and associated glands, bladder/digestive tract,
Human embryo gastrulation
Day 5: Blastocyst embeds into endometrium
Day 14: Primitive streak appears
Day 16: Ingressing cells form early mesoderm
What does the nervous system arise from?
Neuroectoderm
‘Organisers’ for gastrulation found at dorsal lip by cells moving inwards
Birds: Henson’s node
Amphibians: Spemman’s organiser
Mammals: Primitive knot
What is the notochord essential for?
Flexible rod-shaped body comprised of mesoderm derived cells - defines axis of developing embryo
Essential for vertebrate development
Later stages of neuroectoderm formation
- Part of ectoderm adjacent to notochord gives rise to entire nervous system
Spermann and Gold experiment
- Determines localisation of organiser in embryo
- Transplant of newt embryo tissue from one pigmented embryo to non-pigmented embryo
- Induction of two newt embryos fused in middle
What did Spermann and Gold’s experiment prove
Resolved ‘preformation’ and ‘epigenesis’ hypothesis
Preformation - Embryos are just very small formed adults
Epigenesis - Embryo generates new complexity as organism develops
Role of beta-catenin in organiser
Nieukwoop centre - Small piece of tissue next to Spemman’s organiser - induces new gastration site when transplanted into another embryo
- Produces beta catenin
- Vegetal pole cells degrade beta catenin, but animal pole cells do not to form beta catenin gradient
Beta catenin binds TCF3 as transcription factors
Activates twin and siamois genes -> Organiser proteins produced
Wnt signalling
axin/GSK-3/APC destruction complex - proteolytic degradation of beta catenin
- Wnt signalling pathway passes signals from cell surface receptors to control nuclear DNA expression
- Stimulation of receptor releases dishevellled which inhibits destruction complex
- B-catenin enters nucleus to bind TCF transcription factor instead of Groucho to promote expression
Neural inducer molecules
- Notochord diffusible signal -> neural plate development
- Cultured embryonic ectodermal cells undergo neural differentiation
- Ectodermal cultures -> epidermis via BMP4 differentiation
- noggin, chordin and follistatin produced by notochord and inhibit BMP4
- Ectodermal cells above differentiate into neural cells
Neural model of neural induction
BMPs secereted by early embryo -> BMP4 binding TGFbetaR on ectoderm -> Epidermal fate
Notochord -> Chordin, Noggin and Follistatin -> BMP4 binds noggin and noggin binds TGFbetaR -> Neuronal fate
Mouse knockout of chordin and noggin
BMPs not inhibited -> Epidermal fate favoured -> Neural fate not induced
Homozygous mice produced which lack forebrain, nose and facial structures
Neurulation
Neuroectodermal cells form neural plate, with neural crest on each side
Neural plate invaginates to form neural groove, with neural crest located along lips of groove
Neural groove pinches off to form neural tube as two opposing parts of neural crest combine
Neural crest gives rise to peripheral neurons - dorsal root ganglia, sympathetic/parasympathetic ganglia, adrenal medulla
Neural tube form brain/spinal cord
Notochord retained in some more primitive chordates but replaced by spinal cord in higher vertebrates
Adhesion molecules and neural tube formation
Fusion of neural plate requires regulated cell adhesion molecule expression in tissue specific manner
Neural plate switches from E to N-cadherin and N-CAM expressed
Epidermis/neural tissues recognize each other as being same - stops binding
Neural crest cells
Show plasticity
Give rise to sympathetic or parasympathetic neurons depending on anteior-posterior position
Differentiation depends on positional cues
