Congenital Diseases Associated With The CNS Flashcards
What is the first step in CNS formation?
- The first step is the formation of the neural plate
- It’s folding gives rise to the neural tube
- The neural tube then differentiates into: The brain, Spinal cord, Cranial and spinal nerves, eyes and other sensory organs, neural crest
What happens if there is defects in the neural tube formation?
Defects will affect some or all of these structures formed by the neural tube
When does neuralation occur in humans?
Between weeks 3 and 4
Describe the neural tube formation
- The neural plate is initially a flat sheet of cells located along the dorsal portion of the developing embryo
- In direct continuation of with the epidermis and exposed to the extra embryonic medium
- This sheet of cells will become a tube, and will end up being located inside the embryo
What happens as the neural tube closes?
- It becomes patterned along the dorso-ventral and the rostro-caudal axes.
- This process is driven by secreted signalling molecules
- Which promotes the specification of different CNS structures along each axis
List some of the gradual subdivisions of the neural tube along the rostro caudal axis
- Forebrain -> Telencephalon & Diencephalon
- Midbrain -> Mesencephalon
- Hindbrain -> Metancephalon & Myelencephalom
Where does Congenital defects arise from?
Can arise from perturbation of different steps during CNS formation
Briefly describe some of the defects
Describe the closure of the neural tube (PART 1)
- The first step involves the elevation of the edges of a neural plate to form neural folds
- The formation occurs along the midline of what we call the neural group
- Which contains the pressure in everything left in your plate
- In subsequent stages of development, the neural faults will move further when we move towards the midline and they will fuse
Describe the closure of the neural tube (PART 2)
- Essentially in this stage, you go from a flat structure to a folded structure in which the edges of the neural shape is fused together
- This process doesn’t happen simultaneously along the plate but at specific points
- The first point to start closing is on the edge between the hind brain and the spinal cord
- In this region, the closure progresses anteriorly and posterioirly
Describe the closure of the neural tube (PART 3)
- Perturbations in this while step lead to a new reality of the defects that come from defective and neurotic closure
- For e.g. Craniorachischisis. Consists in the complete opening of the neural tube
- This means the first stage of closing doesn’t occur appropriately and the structure remains open
What is it called when the neural tube opening remains only in the anterior portion?
Anencephalic
What is it called when the opening remains in the caudal most region of the neural crest?
Spina bifida
Where does neural closure occur in mice?
- In 3 different places
- Closure 1: located at the end between the hind brain and the spinal cord
- Closure 2: located at the edge between the forebrain and the midbrain (starts a bit later than closure 1)
- Closure 3: Located in the most rostral portion of the forebrain (starts a bit later than closure 2), only progresses posteriorly due to being rostral
Where does neural closure occur in humans?
- Humans have the same closure points as mice but has 2 more closure points in addition
- Closure 4: Occurs more rostral with the hind brain compared to closure 1
- Closure 5: Located in the very posterior portion of the neural plate and progressing on the anterior
What are the 2 modes of the neural plate closure?
- Primary neurulation
- Secondary neurulation
What occurs in primary neurulation?
- Rolling up of the tube
- Closure is by fold apposition then “zipping up”
- Finally is at the cranial and caudal neuropores
What occurs during secondary neurulation?
- Tunnelling or hollowing of the tail bud
- Occurs at the most caudal region of the neural tube
What is the relationship between the primary and secondary neurulation?
- The primary and secondary neural tube becomes continuous
- They fuse with each other
- Located at the region of somites 30-32 in humans
Briefly describe primary neuralation
What are the 2 main processes that are essential for the efficient folding of the neural tube in primary neuralation?
- Shaling of the neural plate occurs by convergence/extension (1)
- Tubing requires bending at hinge points
- Cell wedging at hinge points: Microtubules and actin filaments (2)
What are these processes controlled by from a molecular point of view?
Controlled by the planer cell polarity pathway
Describe the process of convergence-extension (VD)
- A process of lengthening by narrowing, which requires cells to become polarised, in the plane of the cell layer
- They then intercalate amongst eachother
- The structure changes the formation from a broad short tissue to a long narrow tissue (Occurs during the shaping of the neural plate)
What is this process controlled by?
What does it contain?
- Controlled by the wind planer solitary pathway
- Otherwise known Wnt-PCP pathway
- Wnts: Secreted signalling molecules: the ligand
- Frizzleds: Wnt receptor, transmembrane proteins
- Vangl and Celsr: Co-receptors necessary for signal transduction
- Dvl1-3: Cytoplasmic proteins, activated upon interaction between Wnts and Fzds
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