Congenital diseases associated with central nervous system Flashcards
What does the neural tube differentiate into?
brain
spinal cord
cranial and spinal nerves
eyes and other sensory organs
neural crest
When does neurulation occur?
Between weeks 3 and 4
Neural plate initially flat sheet of cells along dorsal portion of developing embryo.
Sheet becomes tube, process driven by secreted signalling molecules.
What is the first step in morphogenesis and closure of the neural tube?
Elevation of edges of neural plate to form neural folds. Formation along midline to form the neural groove.
Subsequent stages of development neural folds move towards midline, will oppose and fuse.
Where is the first point where folding occurs? In what directions does closure progress?
First point at edge between hind brain and spinal cord.
Closure progresses anteriorly and posteriorly, resembles zip.
What neural tube defects can arise when closure of the neural tube doesn’t occur properly?
Craniorachischisis: if very first stage of closing doesn’t occur properly and middle remains open
Anencephaly: opening remains only in anterior portion
Spina bifida: Opening remains in most caudal region of neural tube
What are the five closure points in humans?
First 3 same as in mice.
Closure 1 is at edge between hind brain and spinal cord
Closure 2 is at edge between forebrain and midbrain, closure starts a bit later than closure 1.
Closure 3 is in most rostral portion of forebrain, starts a bit later than closure 2. only progresses posteriorly as it is in the rostral tip
Closure 4 more rostrally within hind brain
Closure 5 at posterior portion of neural plate, progresses anteriorly
What is primary neurulation?
Gives rise to neural tubes
- Rolling up of tube
- Closure is by fold apposition then zipping up
- Finally at cranial and caudal neuropores
What is secondary neurulation?
Tunnelling/hollowing of tail bud, very tip of tube at most caudal region
Primary and secondary neural tubes become continuous, fuse with each other (at sometimes 30-31)
Describe primary neurlation
Neural plate, mediolateral axis broad, rostral caudal axis short
shaping: plate narrows along mediolateral axis, extends along rostral caudal
folding: hinge points estabilished along midline of plate, lateral wings fold, edges of plate closure to midline
convergence: edges of plates further opposed to each other via convergence - hinge points in dorsal regions
Folds fuse, complete closure
What are the two main processes for efficient folding of the neural plate in primary neurulation?
Shaping of the neural plate occurs by convergence/extension
Tubing requires bending at hinge points
Cell wedging at hinge points: remodelling of microtubules and actin filaments
both processes controlled by planar cell polarity pathway
How does convergence-extension lengthen the neural plate?
Occurs during shaping. Lengthening by narrowing. Requires cells to become polarised in the plane of the cell layer.
Cells at edge of tissue intercalate with ones more medially, leads to narrowing of tissue. Tissue elongaes in anterior posterior axis.
From short, broad tissue to long, narrow tissue.
Describe the Wnt-PCP pathway
Wnts bind to Frizzled receptors in membrane of cell
Frizzled receptor undergoes confirmational change, triggers response in cell
Celsr and Vangl transmembrane proteins help frizzled to transduce a signal upon interaction with Wnt
Within cell, Dvl 1-3 activated, partcipate in signalling pathway
Downstream, Dvl 1-3 with other proteins leads to regulation of transcription and dynamics of cell cytoskeleton.
What are the different components of the 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
What mouse mutants in components of the Wnt-PCP pathway show neural tube defects?
Celsr1-/- (crash)
Vangl-/- (loop tail)
Scribble -/- (circletail)
Dvl1/2
Fzd 3/6
in these cases neural plate is abnormally broad with a non-bending region between neural folds - leading to chraniorachischisis.
What is cell wedging and apical constriction?
The mechanism by which hinge points are being formed. Involves change in shape of cells in neural plate so apical side is narrow.
Change in shape lets them work as hinge.
Apical constriction driven by remodelling of cell cytoskeleton at apical cortex of cell.
