Brain Embryology Flashcards
What is the oldest way of looking at the brain in terms of development?
pathology (i.e. preforming surgery on the brain postmortem to see the problem)
- in development, its looking at the anatomy at different stages of development using pathology (i.e. obtaining brain slices at different stages of development)
How can neuroimaging be used to look at brain development?
MRI gives precise picture of the brain and can also be taken in utero to observe the child’s brain and heart developing in the womb
What is the main difference between looking at the brain in development with pathology and MRI vs. looking at it through genetics?
pathology and MRI tells us what happens to the brain development, while genetics is useful to understand what CAUSES the normal/abnormal development
What are some ways that genetics can be used to understand normal and abnormal development?
- through karyotypes which are compacted chromosomes; different bands on chromosomes absorb a color of dye added to it, we look at genetic diseases via looking at matching bands
- when the defects are past the karyotype level then we use the genome wide approach which is a chip that allows you to look at DNA in more details
- Comparative genomic hybridization –> using the WBC of patient to compare to the DNA of control (normal) subjects to see if the patient has deletion of duplication. You mix the control color (i.e. green) with the patient color (i.e. red) and see if it will produce yellow, if it produces RED, it means that the patient has a duplicate, if it produces GREEN it means that patient lacks this gene therefore its a deletion; the next thing to do is check family tree for any known deletion
What are the 7 developmental events that occur in brain embryology? and when do they occur
- Gastrulation (15 days)
- Primary Neurulation (3 weeks)
- Prosencephalic development (2-3 months)
- Neuronal proliferation (3-4 months)
- Neuronal Migration (3-5 months)
- Organization (3 months and beyond)
- Myelination (birth to adult)
What happens during gastrulation?
- first 15 days
- 3 layers of cell form: endoderm, mesoderm and ectoderm. The ectoderm is the neurons and skin
1. the first 6 days after conception, the hypoblast forms
2. on day 8, two layers form: the epiblast and hypoblast
3. the epiblast opens up (it creates a cavity) and inside the cavity is where the migrating cells that form the mesoderm are - the formed mesoderm gives rise to the notochord which is a transient structure (temporary) formed by the mesoderm that will affect the development of ectoderm (the skin and neurons)
What happens during primary neurulation?
- first 3 weeks
- neurulation refers to the formation of the neural tube from a flat layer of ectodermal cells (starts with a sheet of cells and it starts to bend into a tube) the tube is the precursor for the spinal cord and brain
what are the important genes involved in the molecular signaling of neurulation? draw this
TGF-beta
BMP
Sonic hedgehog
- some genes are expressed in dorsal aspect (from the ectoderm) and some in ventral (from the notochord)
SHH is secreted initially from the notochord
How are somites formed in Neurulation phase? Which gene is responsible for the regulation of somites?
somites will form the cartilage of the vertebrae and ribs, muscle of the rib cage, back, limb dermis of the dorsal skin… gene hairy is responsible for the regulation of somites
When does the neural tube close at the end of neurulation?
- needs to close to not have connection of CNS to the outside environment;
- anterior neural pore closes in 24-26 days and the posterior pore closes in 25-28 days
multiple segments close at different times and they close usually before a month after fertilization
What it is anencephaly and spina bifida?
- both conditions when anterior neuropore doesnt close properly (anencephaly) and posterior neuropore doesnt close properly (spina bifida)
both during the neurulation stage
What occurs in the prosencephalic development?
2-3 months in development
- the anterior part of the neural tube splits into 2 prosencephalic vesicles (which end up being the two hemispheres of the brain)
- after 19 days, the three primary brain vesicles: forebrain, midbrain and hindbrain start bulging from the tube
- after 33 days: the telencephalon can be seen (split into two parts) and the diencephalon, mesencephalon, metencephalon and mylencephalon are distinctly bulging out
What is holoprosencephaly? What are the genes known to be associated with this?
its the failure of cleavage of the 2 hemispheres resulting in one big lump and the brain structures that are normally seperated are lumped together
- genes associated with holoprosencephaly is the SHH sonic hedgehod pathway
- the SHH pathway involves patched and smoothened receptors and a second messenger called GLI that results in the transcription of DNA and proliferation (more number of cell growth)
What else forms around 2 weeks of gestation?
the formation of the brain stem which regulates breathing and heart rate
What is Mobius syndrome? What is it the disease of? and what causes it?
it is a congential partial or complete facial diplegia (facial nerve palsy), that involves damage in the cranial nerves for the eyes 6th and 3rd
- and malformation of the limbs called equinovarus (fused fingers)
this is a disease of brainstem development caused by hoxb-1 and hoxb-4 genes during development