Congenital Diseases Associated With Central Nervous System Flashcards
How is the neural plate converted to the neural tube?
Neural plates elevate to form neural folds along the neural groove.
Neural plates fuse together
Morphogenesis occurs and the plates close to form a tube
There are two openings at the end of the tube
- anterior = ancephaly
- posterior = spina bifida
Where are the closures of the cranial and caudal neuropores located on a embryo?
Closure 1: between hindbrain and spinal cord
Closure 2: between forebrain and midbrain
Closure 3: most postural (anterior) portion of forebrain
What are the 2 modes of neural tube closure?
Primary neurulation and secondary neurulation
Both become continuous
What happens in primary neurulation?
Rolling up of the tube
Closure is by fold apposition then “zipping-up”
Finally, at cranial and caudal neuropores
What happens in secondary neurulation?
Tunnelling or hollowing of tail bud
What are the cellular and molecular mechanisms during primary neurulation?
- Shaping of the neural plate occurs by convergence/extension.
- Tubing requires bending at hinge points
- Cell wedging at hinge points: microtubules and actin filaments
Describe the process of convergence-extension
A process of lengthening by narrowing, which requires cells to become polarised, in the plane of cell layer.
What occurs in the Wnt-PCP pathway?
- Wnt (signalling molecule) is a ligand that binds to Frizzles (receptor transmembrane protein)
- frizzles change conformation to trigger a response inside the cell
- The reaction that occurs inside the cell involves bangles and celsr (co receptors necessary for signal transduction)
- Also involved are Dvl-3: which are cytoplasmic proteins activated by the Wnt binding
What happens when there are mutants in components of the Wnt-PCP pathway?
Using mice
The neural plate is abnormally broad with a non-bending region between neural folds - leading to chraniorachischsis.
Describe the process of cell wedging and apical constriction.
The neural plate folds and the notochord forms.
Then the neural crests are elevated
In apical constriction the remodelling of cytoskeleton at the apical cortex of the cell - by the Wnt-PCP pathway localising actomyosin to the apical surface, in a media lateral polarised way.
What is meant by cells in epithelium having apical-basal polarity?
specialised apical membrane facing the outside of the body or lumen of internal cavities, and a specialised basolateral membrane localised at the opposite side, away from the lumen.
What are the 3 most common defects in human neural tube?
Craniorachischisis: faliure closure 1
Anencephaly: cranial neuropores failure
Spina bifida: caudal neuropore failure
What environmental factors effect NTDs (Neuro tubule defects)?
Maternal diet
- vitamin deficiency/malnutrition
- high levels of sugar
- alcohol
Maternal obesity
Diabetes
Hypothermia
Tetratigenic agents
- valproic acid (VPA)
How can folic acid/folate deficiency cause NTDs?
Supplements recommended for pregnant mothers but sometimes it’s not enough.
The deficiency alone is not enough to cause NTDs, usually there is a predisposing mutation (these genes can be involved in folate metabolism or transport OR important for NT closure)
Folate mechanism that lead to NTD unclear
What are some mutations that can occur in folate related genes?
Transport molecules such as FLOR1, SLC46A1
Metabolising enzymes such as GLDC, MTHFD1
