Neurulation Flashcards
What are the first processes that take place within Neurulation (3)
- Development of the notochordal process (from cranial to caudal direction)
- Development of notochord
- from mesoderm
- function: provides axis of symetry (divides the body on left and right), uses signaling pathways to direct stem cells about their place and differentiation
- occurs from middle towards ends
- Definition of neuroectoderm
- cells differentiate into neuroectodermal precursor cells (notochordal signals)
- cells at the midline (above N) thicken -> neural plate (basal and alar plate)
What happens to the Neural plate next? (elaborate on its two phases - what is it made up of, what’s inside/outside of it?)
Neural plate (alar plate) begins to fold inside towards the notochord -> creating Neural groove
- upper part = roof plate (brain)
- lower part = floor plate (spinal cord, hindbrain)
-> Neural groove closes = Neural tube
- middle mecomes ventricular system
- next to it = Somates (precursors od axial muscles and skeleton)
- Formation of neural crest (brain)
Side note: how are somatic stem cells, embryonic stem cells and neuroectodermal precursor cells different?
SSC
- ability of self-renewal
- can generate itself or a variaty of cells within a specific domain (e.g. nervous system)
ESC
- self-renewal
- can generate ALL cells (neural x somatic cells)
NPC
- cannot self-renew
- can only give rise to specific type of cells (e.g. olygodendroglial precursor cell)
What happens to some of the cells from the neural crest?
They start to migrate outside of the neural crest
- the process is governed by the somites around the Neural Tube (mesenchymal cells)
- as they grow out, they’re met with different signals (differentiation)
-> these cells will eventually form = sensory ganglia, autonomic ganglia, adrenal neurosecretion cells, and melanocytes (even cartilage, bones of the skull)
What 2 divisions of autonomic nervous system can you recall? What neurotransmitter mediates it?
SNS = fight or flight, noradrenaline
PNS = rest and digest, acetylcholine
What are stem cells? What have we discovered about them (what construction of cells can do it, iPS)?
= totipotent cells i.e. cells that can differentiate into any type of cell e.g. gametes, nervous system
- blastocysts have this ability (under strict conditions)
- we may also reprogram somatic cells with certain transcription factors = Induced pluripotent stem cells (iPS)
How can we create knock-outs (or knock ins)?
- Take emprionic stem cells from a blastocyst -> place into petri dish and let it grow
- Construct similar but ineffective gene strand
- often attach fluerescent substance to monitor later
- Insert artificial genome into the blastocyst (homologous recombination)
- Select those that “work”
- Insert into a foster mother
- Follow the mating protocol to get a homozygous knockout mouse
How does Conditional knockout/in (CreLox System) work?
- Take emprionic stem cells from a blastocyst -> place into petri dish and let it grow
- Construct LoxP sites surrounding gene of interest
- Insert into blastocyst -> same as regular
=The main difference is that the gene stays normal until a promotor activates the LoxP (which may knock the gene out)
What happens during the development of the neural tube further?
Proliferation of the tube
- two folds occur - Cephalic and Cervical flexure
-> Prosencephelon = front brain
-> Mesencephalon = middle brain
-> Rhombencephaloc = hind brain
-> Spinal cord
What develops from those segments?
-> Prosencephelon
-> Telencephalon = cerebrum (dorsal), basal ganglia, olfactory bulb (ventral)
-> Diencephalon = thalamus, hypothalamus, optic vesicle
-> Mesencephalon = inferior and superior colluculi (dorsal), tegmentum (ventral)
-> Rhombencephaloc = hind brain
-> Metencephalon = pons, cerebellum
-> Myelencephalon = medulla oblongata
-> Spinal cord
Observe how the brain curved up in the cranium:
Repeat what develops from the five segments and add ventricles
What will these parts develop into?
- The upper blue = skin
- Roof plate = induction of sensory neurons
- input to spinal cord
- Floor plate = induction of motor neurons
- output of spinal cord
- Whole in the middle = ventricular system
- Pink = organs
What determines the regional identity within NS (e.g. neurons that correspond to the floorplate)?
Neural tube seems to be divided into equal segments = neurometers
Each segment has a specific combination of Hox genes (in fruitflies Homeobox genes), location they occur, and time of development
- humans have 4 clusters of Hox genes
-> their transcription impacts what signaling molecules will get activated e.g. Sonic Hedgehog in the Floorplate
-> Thus the differentiation
What signaling pathways is hidden under RA? Characteristics? Function?
Retinoic acid (RA) = steroid hormone
- derived from vitamine A
- lipophilic molecule (can easily pass through membranes)
- modulate gene expression (activates or supresses) => cellular differentiation
- too much or not enough A -> neural tube closure failure and other defects of the brain development
What signaling pathways is hidden under FGF? Characteristics? Function?
Fibroblast growth factor (FGF) = peptide hormone
- bind to tyrosine kinase receptor
- alter gene expression via MAP pathway
Function: modulating cell proliferation and differentiation, regulator of fore and midbrain development, regulate spinal cord neurogenesis from the presomatic mesoderm
What signaling pathways is hidden under BMP? Characteristics? Function?
Bone morphogenetic protein (BMP) = peptide hormone
- interacts with surface serine kinase receptor
- transcription regulator via SMAD
Function:
1. Mesoderm = development of bone cells
2. Ectoderm = formation of epidermis
3. Noggin/chordin
- antagonize the surface receptor to which BMPs normally bind -> inactivates their influence -> ectoderm can become neurons instead of skin
Describe characteristics of non-canonical Wnt pathway + its function.
Noncanonical Wnt
- activate receptor protein Frizzled
- regulates transcription via Ca2+, CaMKII
Function: regulates cell movement for lenghtening the neural plate and neural tube, changes cell shape and polarity
Describe characteristics of canonical Wnt pathway + its function.
Canonical Wnt
- frizzled in presence of co-receptor
- beta-catenin is stabilized and binds to LEF/TCF and influences gene espression
Function: Influences cell proliferation, adhesion and differentiation AFTER gastrulation and neurulation finishes
What signaling pathways is hidden under Shh? Characteristics? Function?
Sonic Hedgehog (Shh) = protein hormone
- interacts with surface bound receptors
- patched in the presence of smoothened
-> Switch in the transcription factors
- No Shh: Gli 3 inhibits transcription
- With Shh: Gli 1 available to regulate gene expression
- Important for: closing of neural tube, identity of motor neurons (ventral sinal cord, hindbrain)
