L17 - Congenital Diseases associated with the Central Nervous System Flashcards
When does Neurulation begin to take place?
At week 3 of embryogenesis
Describe the process of Neurulation including the timeline?
End of the 3rd week:
The lateral edges of the ectoderm become more elevated and will form the Neural fold. The depressed mid-region that arises from this is called the neural groove.
This layer is now called the Neural plate.
Neurulation advances both Cranially and Caudally to give rise to the brain and the spinal cord respectively
Neural fold on each end will then fuse with each other to form the Neural tube.
The ectoderm at each end will then move downwards to surround the endoderm and the mesoderm
By the end of week 4:
The Neural tube has formed.
Some of the ectodermal cells from the neural tube migrate to form several layers of cells called the Neural crest. The Neural Crest gives rise to many structures that work with the CNS, like spinal and cranial nerves and their ganglions, autonomic nervous system ganglions and meninges.
The remaining ectoderm will form the skin
During the rest of embryology and development:
Neural tube develops in sections
Spinal cord - becomes the spine.
Rhombencephalon - becomes the pons, cerebellum and the medulla.
Mesencephalon - becomes the mid-brain.
Prosencephalon - becomes the cerebrum and thalamus.
What does the spinal cord become in Neurulation of Embryology?
Spinal cord - becomes the spine.
What does the Rhombencephalon become in Neurulation of Embryology?
Rhombencephalon - becomes the pons, cerebellum and the medulla.
What does the Mesencephalon become in Neurulation of Embryology?
Mesencephalon - becomes the mid-brain.
What does the prosencephalon become in Neurulation of Embryology?
Prosencephalon - becomes the cerebrum and thalamus.
How many closure points of cranial/caudal neuropores exist in humans and where are they located?
There are 5 closure points:
1 - cranio-rachisis (between hindbrain and spinal cord)
2 - anencephaly (between forebrain and midbrain)
3 - rostral portion of the forebrain
4 - rostrally in the hindbrain
5 - spina bifida (posterior portion of neural plate at the end)
What is Primary Neurulation?
rolling up of the tube
closure is by fold apposition then zipping-up.
Finally closure at cranial and caudal neuropores
What is Secondary Neurulation?
tunelling or hollowing of the tail bud.
What 2 mechanisms are required for Primary Neurulation?
CONVERGENCE/EXTENSION:
allows for the shaping of the neural plate
CELL WEDGING:
occurs at hinge points to aloow tube to bend. Involves remodelling of the microtubules and actin cytoskeleton of cell
Describe the process of Convergence and Extension of primary neurulation?
A process of lengthening by narrowing, which requires cells to become polarised in the plane of the cell layer and intercalate amongst each other.
flat sheet of cells become intercalated with each other, which leads to a narrowing of tissue as well as elongation. Changes from broad tissue into long and narrow tissue.
Describe how the Wnt-PCP pathway controls process of convergence and extension?
Wnts are the secreted ligand/signalling molecule which bind to the Frizzled transmembrane receptor.
The frizzled receptor undergoes a conformational change upon binding of Wnt, which then triggers a response within the cell.
Vangl and Celsr are Co-receptors that are necessary for signal transduction - they help Frizzled receptor to induce changes downstream.
The first target of this signalling is a membrane complex Dishevelled, which becomes activated.
Further downstream signalling causes transcriptional changes in Nucleus, as well as the dynamics of the cell cytoskeleton.
What is Craniorachischisis?
Its a congenital malformation which arises from incomplete closure of the neural tube. There is also an absence of bending regions between neural folds and the neural plate is abnormally broad
Describe the process of cell wedging?
done by remodelling the cell cytoskeleton at the apical cortex to form rounded hinge. Cells have apical-basal polarity
The Wnt-PCP pathway is also involved in this mechanism. It localises the actomyosin to the apical surface in a mediolateral polarised way. It contracts on the mediolateral axis, which leads to a change in the shape of the cell, and the formation of hinge points.
Describe maternal diet as an environmental factor associated with Neural tube Defects?
Vitamin deficiency and malnutrition:
- folate deficiency (prevents closure of neural tube)
- inositol deficiency (higher risk of NTDs)
- high levels of sugar
Maternal Obesity and Diabetes (high risk of NTDs)
Hyperthermia (high temperature increases risk of NTDs)
Teratogenic agents:
- valproic acid
