Development p1 Flashcards
What is neural induction
The process where embryonic cells in the ectoderm are induced to acquire a neural fate, forming the neural plate
What does the neural plate eventually give rise to
Central and peripheral nervous system
What is gastriulation
Creation of a gastrula, forming the 3 distinct germ layers
What is the important organising centre that controls neural induction
The dorsal blastopore lip of the gastrula
What did Spemann and Mangold show the dorsal blastopore lip of the gastrula induces
The formation of a body axis
What does the dorsal blastopore lip later form
The dorsal mesoderm
What study did Spemann and Magold do
Transplanting a second dorsal blastopore lip into a salamander gastrula induces host tissue to form a secondary body axis -> entre nervous system
What is the ‘default’ fate of ectoderm cells in neural induction
Neural diffentiation
What do proteins secreted by the dorsal blastopore lip
Act as BMP antagonists, de-repressing neural differentiation
What prevents ectoderm cells achieving their ‘default’ neural differentiation fate
Neighbouring ectoderm cells synthesize and secrete BMPs, suppressing potential for neural differentiation and promoting epidermal differentiation instead
What are examples of proteins secreted by the dorsal blastopore lip that act as BMP antagonists
Noggin, Wnt chordin, follistatin
What chemicals act as intermediaries in neural differentiation (Pankratz)
Transcriptino factors of the SoxB family, expressed in prospective neural plate cells
What growth factors are necessary for neural differentiation other than BMP antagnosist
Ectoderm cells must be exposed to fibroblast growth factors
What results from disorders of neural induction
Abnormalities in forming the body axus can cause dicephalic parapagus- a rare form of conjoined twins
What is neural patterning
Process by which cells in the developing nervous system acquire distinct identities according to their specific spatial positions
What do the rostral vs caudal regions of the neural plate secrete
Mesoderm in caudal regions- high Wnt levels
Endoderm in rostral region- proteins that inhibit Wnt
What gradient controls rostral caudal patterning in the neural plate
Gradient of Wnt- high at caudal, low at rostral
What additional signals refine the rostrocaudal pattern other than Wnt gradient
Anterior neural ridge (ROSTRAL)- secretes FGF, forms telencephalon
Mesoderm at CAUDAL levels- secretes retinoic acid and FGF, forms subdomains of hindbrain and spinal cord
What 2 specialised cell groups in the neural tube refine the ROSTROCAUDAL PATTERN
Zona limitans intrathalamica (diencephalon), isthmic organiser (hind/mid brain boundary)
What does the zona limitans intrathalamica do
Secretes sonic hedgehog that causes nearby cells to form thalamic nuclei
What does the isthmic organiser do
Specifies the neuronal subtypes within the hind- and mid- brain ie DA neurons in midbrain, 5HT neurons in hindbrain
Secretes Wnt 1 and FGF8
Describe the different domains either side of the midbrain-hindbrain boundary
Cells either side express different Hox genes and different homeodomain transcription factors, that control the expression of signalling factors like Wnt, FGF, Shh
Describe the role of Hox genes in rostrocaudal patterning
Rostrocaudal differences in Hox gene expression determine the identity of neurons in different rhombomeres
What are rhombomeres
Rostrocaudal segments of the developing hindbrain
What develops from the different rhombomeres
Different cranial nerves emerge from each rhombomere
What type of cells form from the dorsal neural tube
Sensory neurons, local circuit interneurons, neural crest cells
What type of cells form from the ventral neural tube
Motor neurons and interneurons
What provides ventral patterning signals
First notochord, then floorplate
What is the notochord
Mesodermal cells group directly under the ventral neural tube
What provides dorsal patterning signals
First epidermal ectoderm spanning the dorsal midline, then the roof plate
What are the roof and floor plate
Glial cell groups
What do the notorchord and floor plate secrete for ventral patterning
Sonic hedgehog
What is sonic hedgehog
A morphogen- can direct different cell fates at different concentrations
What gradients determine ventral patterning
Ssh ventral->dorsal gradient in the ventral area
Corresponding gradient of Gli transcription factor
What is Gli transcriptino factor
Usually prevents Shh activation
What is the result of the Ssh Gli ventral gradient
Different homeodomain transcriptino factors repressed in different regions -> different differentiation -> 5 cardinal progenitor domains and 5 classes of ventral neurons
What occurs first in dorsal patterning
Epidermal cells in the midline release BMP4, which triggers differentiation of root plate
What occurs in dorsal patterning once the neural tube closes
Roof plate cells express BMP and Wnt proteins eg BMP4
What does BMP4 do when secreetd by the roof plate
Induces differentiation of neural crest cells, then generation of sensory neurons
What does Wnt protein do when secreted by the roof plate
Promotes proliferation of progenitor cells in the dorsal neural tube
What is neurulation
The folding of the neural plate into the neural tube
Examples of mechanisms invovled in neurulation
Transcription regulation, proteases, antagonistic interactions between BMPs/SSh/Noggin
What disorders result from mutations in the Shh dorsoventral pathway
Defects in ventral forebrain structure development, spina bifida, limb deformities, cancer
What is spina bifida
Spine and spinal cord don’t form properly, neurulation messed up
What disorders result from the caudal end of the neural tube not closing properly
Spinal dysraphism (conditinos affecting the spine/spinal cord/nerve roots) eg spina bifida
What disorders result from the rostral end of the neural tube nto closing properly
Anencephaly, inionschisis
What is anencephaly
Absense of a major portion of te brain, skull and scalp
What is inionschisis
Failure of the neural tube to close in the occipital region
What region is involved in generating neural cells
Proliferative zones surrounding the ventricles
What are progenitor cells
Cells in the vetricular zone of the neural tube, proliferate rapidly in early embryonic development, have stem cell-like properties
What is asymmetrical cell division
Progenitor produces a daughter that retains cell-like properties, and one differentiated daughtter
What is symmetrical cell division
neural stem cells divide to form 2 stem cells, expanding the population of proliferative progenitor cells
What are radial glial cells
The earliest distinguishable cell type in the neural epithelium, progenitor cells
What can radial glial cells do
Generate neurons and astrocytes, undergo asymmetric and self-renewing cell division
Describe how the different parts of radial glial cells are spread out
Cell bodies in the vetricular zone, long-processes end in the pial surface- remain attached to these surfaces as the brain thickens
How are radial glial cells important in cell migration
Serve as a scaffold for the migratino of neurons emerging from the ventricular zone
What cell-surface signallingsystem determines the fate of radial glial cells
Involves transmembrane ligand delta and its receptor Notch, which regulate a cascade of basic helix-loop-helix transcription factors
What happens to radial glial cells with low vs high Notch activation
LOW- neurons
HIGH- radial glial cells, astrocyctes, oligodendrocytes
What antagonises Notch signalling
Numb, a cytoplasmic protein that antagonises Notch signalling
What does Numb do
Expressed in neuronal daughters of dividing progenitors, allows glial cells to avoid exposure to Notch signals, and develop into neurons
What are the 3 main stages of cerebral cortex development
Preplate, cortical plate, mature pattern of layers
Describe how neurons migrate along radial glial fibres
Neurons in the preplate extend a leading process to wrap around the radial glial cell, settling in the cortical plate
What happens in cerebrla cortex migration once the cortical plate is formed
Neurons continue migrating, forming cortical layers in an inside-first, outside-last way
What other ways can cells migrate than using radial glial cells
Can migrate using pre-existing axonal tracts, neural crest cells undergo free migration throughout the body
What are filopodia
Extensions from growth cones, detect attractive/repellant directional cues from the environment with surface receptors
How do growth cones respond to directional cues
Transduce these cues into signals that regulate their cytoskeleton, acting as motor structres to drive axon elongation
What can intracellular signals in the growth cone do
Alter the growth cone’s response to growth factors as either attractor or repellant
What proportion of neurons generated in the nervous system are lost
Half
What is the neurotrophic factor hypothesis
Cells at a neuron’s target site secrete a small amount of a trophic factor, uptake by a neuron suppresses a latent death program in that neuron
How are cells programmed to die without neurotrophic growth factor
Apoptosis
How do neurotrophins work
Bind to receptors on nerve terminals, internalised, activate signalling pathways and transcription programs necessary for survival
What disorder can issues duringc cell generation cause
Microcephaly- baby’s brain does not develop properly, causing small head
What disorders can defective neuronal migration cause
Lissencephaly, periventricular heterotrophia
What is periventricular heterotopia
Neurons don;t migrate properly, form clumps around the ventricules
How does the eye develop from the diencephalon
Inner layer-> neural retina
Outer layer-> pigmented epithelium
Subarachnoid space extends to the optic disk
What substance presumbly prevents spina bifida
Folic acid
What are homeotic genes
Genes that, when mutated, cause conversino of one part of the body into another
Zika?
Zika causes microcephaly/corpus callosum agenesis/lissencephaly IF caught by mama in the first trimester
What are sites of adult neurogenesis
Subventricular zone, dentate gyrus
What things suggest our neurons are the very old
No mitosis of mature neurons, very limited neurogenesis in cerebral cortex, limited sites of adult neurogenesis
What are the 2 major areas of tangential migration
Neurons in the medial ganglion eminence migrate to the neocortex to form interneuron populations
Neurons in the lateral ganglion eminence migrate rostrally to contribute to interneurons of the olfactor bulb
How do neural crest cells first leave the neural tube
BMP signalling causes cells to break down the basement membrane surrounding the neural tube epithelium, and delaminate from the neural tube
What internal change happens to neural crest cells ocne they delaminate from the neural tube
Cell adhesino protein expression changes, meaning they lose adhesive contacts with neural tube cells
Begin to express integrins, receptors for proteins found along migratory paths
What path do neural crest cells take towards the periphery
Pass through the anterior half of somites, as proteins in their posterior half repel them- some remain here OR some go dorally around the somite
What happens to neural crest cells that stay in the anterior somite half
Differentiate into sensory neurnos of the DRG, dependent on Wnt signals and bHLH factors
What happens to neural crest cells that go dorsally aruond the somite
These cells are exposed to BMPs and develop as symapthetic NA neurons
What does the endoderm give rise to
Gut tube, lungs, pancreas, liver
What does the mesoderm give rise to
Muscle, connective tissues, vasulcar system
What does the ectoderm give rise to
Skin, neural plate
What do somites give rise to
Muscle and cartilage
What transcriptino factors are expressed in the forebrain/midbrain vs hind brain
Forebrain/midbrain- Otx2
Hindbrain- Gbx2
