Neural Development - Development of precursor cells, differentiation into immature neurons and glial cells Flashcards
How is the human morula formed?
= morula formed by cell division from the zygote
= contained within zone pellucida (cannot expand) so no growth in size yet
= in latter compaction stage, individual cells become less distinct
= compactions = cells adhere together + have gap junctions
(ion / molecular exchange between cells)
What do Embryonic Stem Cells form? Where are they formed / located?
= everything!
Morula (day 4)
= cells (blastomeres) secrete fluid and outermost cells become tightly bound together
= process called compaction
Blastocyst / Blastula (day 5)
= inner cell mass or embryoblast forms embryo
= inner cell mass is source of pluripotent embryonic stem cells
= they give rise to all adult structures, including nervous system
= trophoblast later forms placenta
= has polarity (embryonic pole)
First is binary fission
= NOT regulated by spatial cues
= BUT by the cellular expression of specific transcription factors
Early blastula
= cells are totipotent = can form anything
ICM cells
= begin to form the bilamminar disk
= epiblast cells near the trophoblast cells
= hypoblast cells near cavity
What does Gastrulation form?
= the primary germ layers (3)
Epiblast cells
= from the inner cell mass converge and the middle + ingress at the primitive streak
Two layers = epiblast and hypoblast
= are transformed into 3 layers:
= ectoderm
= mesoderm
= endoderm
Gastrulation also creates the antero-posterior body axis
What does Gastrulation in a chick embryo look like?
In the chick embryo
= appearance of Koller’s sickle is the first sign of gastrulation
= Hensen’s node is the ‘organiser’ for the process of infolding during gastrulation
= order in which cells enter the blastocoel through Hensen’s node determines their specification in the embryo
(1st cells = endoderm, 2nd cels = mesoderm, 3rd cells = ectoderm)
= Gastrulation forms the 3 primary germ layers (conserved process)
What do the 3 Germ Layers form?
Ectoderm (outside)
= form skin, nails, hair, lens of eye, lining of internal and external ear, nose, sinuses, mouth, anus, tooth enamil, pituitary gland, mammary glands
= and ALL parts of the NERVOUS SYSTEM
Mesoderm (middle)
= form muscles, bones, lymphatic tissue, spleen, blood cells, hear, lungs and reproductive and excretory systems
Endoderm (inside)
= lining of lungs, tongue, tonsils, urethra and associated glands, bladder and digestive tract
What does Gastrulation in the Human Embryo look like?
Day 5
= blastocyst (bilaminar = epiblast and hypoblast)
= embeds itself into the endometrium (womb lining)
Day 14
= primitive groove (streak) appears
Day 16
= ingressing cells start to form early mesoderm
(nutrients through placenta , rather than yolk in chick)
(still has the node, BUT primitive streak is called primitive groove)
Where does Nervous System arise from?
= the Neuroectoderm
(subsection of the ectoderm)
= cells move inwards from the node that organises gastrulation
Notochord
= formed from mesoderm
= has essential role in vertebrate development
= defines axis of developing embryo
(dorsal, ventral, head, tail)
The ‘organiser’ for gastrulation is found at the dorsal lip
= in birds = Henson’s node
= in amphibians = Spemman’s organiser
= in mammals = primitive knot (or node)
The part of the ectoderm adjacent to notochord
= will give rise to the entire nervous system
In chordates
= notochord persists throughout life
In vertebrates
= notochord goes on to form parts of vertebrate and spinal cord
Endoderm
= also begins to inavaginate to start to produce the digestive tract
How was the vital role of the organiser in embryogenesis confirmed?
= Spemann and Mangold experiments
= experiment to determine the localisation of the organiser in the embryo
= transplant of newt embryo tissue (dorsal lip of blastropore) from one pigmented embryo into non-pigmented
= induced 2 newt embryos fused together in the middle
= contradicted / resolved 2 hypotheses
= Performation = that embryos are just very small fully formed adults
= Epigeneseis = embryo generates new complexity as organism develops
What is the molecular basis of the organiser?
= β-Catenin
Nieukwoop Centre
= next to Spemman’s organiser
= capable of inducing a new gastrulation site when transplanted into another embryo
= produces β-catenin
= cells in vegetal pole = degrade β-catenin
= BUT cells in animal pole = do NOT
= therefore β-catenin diffusion gradient across the embryo (stabilised at dorsal end)
= promotes action of β-catenin in the Spemmans organiser
= β-catenin binds to TCF3 = acts as a transcription factor
= activates the expression of genes such as twin + siamois that promote synthesis of other ‘organiser’ proteins
What does Wnt signalling do?
= regulates β-catenin and neural development
The axin/GSK-3/APC ‘destruction complex’
= normally promotes the proteolytics degradation of β-catenin
= Wnt signalling pathway passes signals from surface receptors (e.g. Frizzled) to control DNA expression in the nucleus
= stimulation of the receptor molecule releases Dishevelled (Dsh)
= which inhibits the ‘destruction complex’
= β-catenin can now enter nucleus and form another complex that binds to DNA and turns on expression of key organiser genes
What are the Neural Inducer Molecules?
Diffusable signal
= from notochord causes the cells above to develop into neural plate
= cultured embryonic ectodermal cells under neural differentiation = ?default neuronal cell fate
Action of BMP4 (bone morphogenic protein 4, TGFβ family)
= induces ectodermal cultures to differentiate into epidermis
= BMP4 inhibits differentiation into neural cells in vivo (inhibits default neuronal cell fate)
During neural induction
= noggin, chordin and follistatin
= are produced by the notochord and inhibit BMP4 acticity
= causing ectodermal cells above to differentiate into neural cells
What do mouse KO of Chordin and Noggin show?
BMPs not inhibited
= so epidermal fate not inhibited
= neural fate in not induced
Homozygous mice produced which lack forebrain, nose and facial structures
What is neurulation?
= neural plate induction
- Neuroectodermal cells form the neural plate
= with neural crest on either side - Neural plate invaginates to form neural groove
= with neural crest located along lips of groove - The neural groove pinches off to form the neural tube
= as two parts of the neual crest combine
Neural crest will eventually give rise to:
= neurons of the peripheral nervous system
= dorsal root ganglia
= sympathetic and parasympathetic ganglia
= adrenal medulla
Neural tube
= will form into the brain and spinal chord (CNS)
Notochord
= retained in some primitive chordates (e.g. hagfish and lampreys)
= but in higher vertebrates = replaced by the vertebral column
What are the Cell Adhesion Molecules in Neural Tube Formation?
Fusion of neural plate
= requires regulation of cell adhesion molecule expression in a tissue specific manner
Neural plate switches from E-cadherin
= to N-cadherin and N-CAM expression
Epidermis and neural tissues
= can now recognise each other as being the same
= (homophilic adhesion)
= stops binding of neural tissue to epidermis
How was is shown that Neural Crest Cells show Neuronal Plasticity?
= transplantation experiments
cells of neural crest show Plasticity
= can give rise to either sympathetic or parasympathetic neurons
(depending on their anterior-posterior position)
= differentiation depends on positional cues
Anterior
= gives rise to parasympathetic neurons
(acetylcholine)
Posterior
= gives rise to sympathetic neurons
(noradrenaline)
What is neural tube stem cell proliferation? What happens in replication?
Neural tube stem cells
= give rise to all CNS nerve cells, astrocytes and oligodendrocytes
Replication occurs
= in the ventricular zone of the neural tube (close to the lumen)
During replication
= the stem cells migrate through the neural tissue
Daughter cells
= can remain to generate more progeny cells
OR
= can migrate out to form neurons or glial cells
How are radial glial cells formed?
Under influence of genes
= e.g. FOXG1, HX2, PAX6, EMX2
= neural stem cells produce radial glia
= which extend a process from the ventricle all the way to the pial surface
