#4 Embryology Flashcards
What does the study of embryology study? Why is it important?
How we get from a single cell as a fetus, to an entire brain. Important because defects in this brain development can lead to neurological disorders (epilepsy, autism, learning/intellectual disabilities, brain cancer)
What are the three ways we learn about brain development/
- Pathology: the structure of the brain, how the brain works, oldest method used
- Neuroimaging: MRI, can be performed on living patients at multiple times, can look at brain activity during different stages of development (in utero)
- Genetic testing: more used in diagnosis of brain malformation (pre and post-natally)
What are the three main divisions of the brain?
The cortex (telencephalon), the brainstem (rhombencephalon), and the cerebellum (mini brain).
What are the 7 major steps in brain embryology?
- Gastrulation
- Primary neurulation
- Proencephalic development
- Neuronal proliferation
- Neuronal migration
- Organization
- Myelination
What is the first step in brain embryology? What happens within this step?
Gastrulation.
Here we get the formation of the three layers of cells, the endoderm, mesoderm and most importantly the ectoderm which contains the neurons and skin.
Here we get neurocutaneous syndromes/disorders which affect the ectoderm and development such as neurofibromatosis I and tuberous sclerosis (learning disability, seizures, ash spots on face)
What is the second step of brain embryology? What happens here?
Primary Neurulation
Here the layers of cells become folded into a tube with an opening at each end for the head/brain and the spinal cord. The anterior neuropore should close after 24-26 days, and the posterior should close after 25-28 days. The genes involved here include TGF-beta, SHH (released from notochord ventrally), and BMP (released dorsally)
What are the two disorders that result from the failure of the anterior neuropore and posterior neuropore to close? Which is more serious? Is there any preventative measures that can be taken?
Anencephaly: failure of the anterior neuropore to close, usually not compatible with life
Spina bifida: failure of the posterior neuropore to close, not always visible, can live with it, there are surgical remedies, and if mothers take folic acid supplements to increase their FA this is preventative to spina bifida
What is the third step in brain embryology? What happens here?
Prosencephalic development.
The anterior part of the neuropore splits into 2 prosencephalic vesicles, then splits into three primary vesicles (fore/mid/hind brain), and then into five secondary vesicles (cortex, brainstem, spinal cord, cerebellum, diencephalon)
What is holoprosencephaly? What stage of development is it part of?
It is the failure of cleavage of the two hemispheres, associated with the SHH pathway in the notochord. This pathway involves pathched and smoothed receptors, and a second messenger called GLI that results in transcription of target DNA and proliferation.
At what point in development do you get formation of the spinal cord?
2 weeks
What is facial nerve palsy?
No voluntary control over the facial muscles, eyes are not straight, cannot smile correctly
What is mobius syndrome?
Congenital partial OR total facial diplegia, other cranial nerve palsy, get malformation of limbs (equinovarus), disease of brainstem development and the cause is Hoxb-1 and Hoxb-4
What are the homeobox genes?
Three scientists found the family of genes responsible for embryo partitioning in flies, and these have also been found in the human brain and spine patterning
What is the fourth step in brain embryology? What are a few proliferation related disorders (3)?
Neuronal Proliferation
This involves proliferation of neurons so the brain becomes thicker (not just a tube).
Hemimegalencephaly: one hemi become much thicker than the other side due to excess proliferation on one side
Tuberous sclerosis: due to mutation in the tuberous sclerosis genes, leads to abnormal mass formation, disease of the skin and brain, genes associated with it are TSC-1 and TSC2, see intellectual disability, epilepsy and autism. Some patients get subependymal giant cell astrocytoma (SEGA) but only 6-14%, and this blocks drainage and leads to death
Microcephaly: lack of proliferation, head circumference is normal at birth but fails to progress normally, due to mutations in the FOXG1 genes
What is the fifth step in brain embryology? What happens here? What are two disorders that come about via this step?
Neuronal Migration.
Neurons are born in the periventricular zone (just outside the ventricles), and then they migrate towards the brains surface along progenitor cells (eventually differentiate into glia) and this is called inside out migration. Defects in neuronal migration results in neurons staying close to the ventricles and leads to x-linked
