Neural Induction Flashcards
What characteristics of zebrafish make it a good model organism for studying developmental biology?
- genetics are easy to modify
- transparent while they develop, so they are easy to image
What characteristics of C. elegans make it a good model organism for studying developmental biology?
- simple and well-understood
- well-characterized nervous system
- transparent while they develop, useful for imaging
- short life cycle which makes them easy to manipulate genetically
Why are mice used as a common model organism in developmental biology?
- closely related to humans
- good models for disease
- easy to perform behavioural experiments on them
Why are Xenopus laevis commonly used to study developmental biology?
- easy to find in the wild
- easy to get gametes from and easy gametes to grow in a dish
- have large eggs - optimal for injection and heal quickly
- eggs develop externally - easy to harvest
In the blastula stage, why are the cells at the animal pole smaller than the cells at the vegetal pole?
Animal pole cells have been cleaved more times
There is very little transcription of different genes in the xenopus embryo until this developmental stage
The mid blastula stage
Describe the cleavage of the cells of the xenopus blastula
Rapid synchronous cleavage which happens radially
The blastocoel appears at this stage in embryonic development
Blastula stage
What is specified by the end of the late blastula stage?
3 germ layers
At the end of the late blastula stage, what are the 3 groups of cells present, and what are their cell fates?
- animal cap cells > ectoderm
- marginal cells > mesoderm
- vegetal cells > endoderm
What is a key difference in the early development of xenopus and humans?
Humans have equivalent structures to amphibians, but we have a flat sheet of cells as opposed to a sphere of cells
Which population of cells slides under the dorsal lip during the cellular reorganization of gastrulation?
Animal cells
Why is the generation of asymmetry relevant at the blastula stage?
Generation of asymmetry is the basis of later cellular fate determination
The ectoderm later goes on to become these 2 important systems
Epidermis
CNS
What is the ultimate cell fate of the cells which make up the blastula mesoderm?
Will become muscle and blood cells, among other “middle body” cells
What is the ultimate cell fate of the cells which make up the blastula endoderm?
Cells of the gut
Describe neurulation
A flat sheet of neural tissue-destined cells fold into the neural tube to establish what will later be the notochord
At what stage is the anterior posterior axis established?
Gastrulation
The neural plate stages coincides with this embryonic phase
Late gastrulation
Which stages follows gastrulation?
Neurula stage
At what stage does the neural-fated tissue go underneath epidermal-fated tissue?
Neurula stage (after neural tube formation)
Formation of the neural tube is driven by changes in…
Planar cell polarity
What is the medial hinge point (MHP)?
The hinge point at which the neural plate folds during formation of the neural tube
Spina bifida is usually a condition associated with improper…
Neural tube closure
How is folic acid thought to be involved in spina bifida?
A lack of dietary folic acid may result in downstream misregulation of factors which are regulated by folic acid, and which are involved in neural tube closure
After the neural tube closes, cells of the neural crest…
Delaminate from the dorsal neural tube and migrate elsewhere
Neural crest cells eventually give rise to…
The peripheral nervous system (sensory nerves and ganglia)
Neural crest cells also give rise to…
Bone, pigment cells, cartilage, connective tissue, endocrine cells
Why are cells of the neural crest sometimes referred to as the “4th germ layer”?
Even though the cells give rise to neural tissue, they also give rise to a range of other tissue types
What kinds of animals have neural crest cells?
Vertebrates
The development of the trigeminal ganglion in humans forms…
Sensory neurons of the face
The neural crest eventually gives rise to this part of the nervous system
The PNS
The neural tube eventually gives rise to this part of the nervous system
The CNS
In early human brain development of the neural tube, there are 3 primary vesicles which can be referred to as…
Forebrain, midbrain, and hindbrain
After the 3 vesicle stage of neural tube development, there is further subdivision of the forebrain midbrain and hindbrain into… (5)
Telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon
The telencephalon later gives rise to these adult derivatives in humans
Olfactory lobes, hippocampus, cerebrum
The diencephalon later gives rise to these adult derivatives in humans
Optic vesicle, epithalamus, thalamus, hypothalamus
The mesencephalon later gives rise to these adult derivatives in humans
Midbrain
The metencephalon later gives rise to these adult derivatives in humans
Cerebellum and pons
The myelencephalon later gives rise to these adult derivatives in humans
Medulla
Dorsal patterning of the neural tube mostly happens through morphogen gradients of…
Shh
What is the overall purpose of gastrulation?
Establish the 3 germ layers, tissue becomes regionalized into dorsal-ventral axis
Describe involution
A type of cell movement which drives gastrulation, in which cells migrate under the dorsal blastopore lip
What does the blastocoel become in a fully developed vertebrate?
Becomes the inner cavity of the gut (does not give rise to a structure, rather, gives rise to a lack of structure)
Involution can be initiated due to changes in cell… (2)
Adhesion and morphology
Gastrulation begins on the (dorsal/ventral) side of the embryo
Dorsal
In deuterostomes, gastrulation begins on the (anterior/posterior) embryo
Posterior
The anterior neural tube eventually becomes this part of the CNS
Brain
The posterior neural tube eventually becomes this part of the CNS
Spinal cord
The yolky endoderm present in the neurula stage will eventually give rise to…
The structures of the gut
What is the energy source of a young tadpole in the beginning stages of its life?
Yolky endoderm
Describe the motility of a young tadpole while it is living off the yolky endoderm
Will not be motile, sitting around
Define a fate map
Map that outlines what a cell or tissue at an early stage of development will eventually become at a later stage of development
How could you develop a fate map?
Stain different parts of the embryo with dyes on agar (use landmarks like the dorsal lip) then investigate the location of the dyes at a later stage of development
Alternatively: can do genetic fate-mapping now with GFP/fluo dyes
Describe the famous experiment which determined when neural and epidermal cell fates are specified. What were the key findings?
Spemann/Mangold experiment:
Transplanted presumptive neural ectoderm and attached it to host embryo to see if it could induce formation of a secondary neural plate
Early gastrula extraction + transplant: became epidermis (did not induce neural fate)
Late gastrula extraction + transplant: became neural tissue
Therefore, something must be happening during this phase to induce neural fate
How could you design an experiment to test when neural and epidermal cell fates are determined?
Extract different regions of tissue at different stages and try to grow them independently
What is the “default state” of the animal cap (dorsal) at the early gastrula stage?
Epidermis
What is the default state of the ectodermal tissue, epidermis or neural tissue? Why?
Neural tissue: because ectoderm becomes epidermis with BMP signaling, if tissue is grown in culture without BMP, will become neural
Describe where in the embryo the organizer is
In the dorsal mesoderm
What is the general role of the organizer?
Secrete BMP antagonists to induce formation of neural tissue
The structure responsible for formation of the organizer is called the…
Nieuwkoop centre
During the Spemann/Mangold experiments, describe which tissues (donor and host) are exhibiting neural fates and describe why this is important
Donor tissue becomes part of the neural tube, and the surrounding tissue which is also neural is from the host
This is important because it demonstrates that it is not just the host tissue becoming neural, the donor tissue is also able to induce neural fates in the surrounding host tissue = must be secreting neural inducing factors
If only neural inducing factors are eliminated from an embryo, what is the default state of the dorsal ectoderm?
Epidermis
If both neural inducing factors AND BMP are eliminated from an embryo, what is the default state of the dorsal ectoderm?
Neural
Describe the theoretical basis of the Smith and Harland 1992 “fishing experiment.” What important molecule did they discover?
Used LiCl on xenopus embryos > this results in highly dorsalized embryos = excess of “dorsal genes”
Combined mRNAs from dorsalized and wild-type embryos, the like mRNAs will combine to each other and be subtracted, leaving behind the excess genes of the dorsalized embryos
Found noggin
Describe Occam’s razor?
The simplest theory or idea is often the correct one
Correlative studies on noggin by Smith and Harland demonstrated that noggin may be a good candidate gene for a neural inducing factor because…
It is expressed in the expected location at the right time
Briefly describe how the “odd-skipped” method of in situ hybridization works
mRNA probes are synthesized with DIG groups on them, which upon binding to the target mRNA are capable of catalyzing a reaction with a dark substrate, allowing visualization of the mRNA
How does noggin inhibit BMP signaling?
Binds to BMP ligand, sequestering it
BMP is a member of this family of signaling molecules
TGF-beta
Heterodimers of receptors in the TGF-beta signaling family commonly activate this downstream protein
Smad 2,3, which activates Smad 4 (Smad dimerization)
When Smad 2,3 and Smad 4 dimerize, what happens?
The complex is capable of entering the nucleus and can activate or repress transcription
BMP activates these downstream signaling molecules
Smad 1,5 and Smad4
What is a key source of BMP inhibitors in vertebrate development?
The organizer
Signaling from this molecule in this tissue layer helps in formation of the organizer
Beta-catenin from the dorsal endoderm
Beta-catenin and this other molecule are secreted from this centre, resulting in formation of the organizer
Wnt from the Nieuwkoop centre
Involution is driven by this population of cells
Bottle cells
