Neurulation Flashcards
(14 cards)
How is the AP (anterior-posterior) axis established during neurulation in Xenopus?
- maternal signals localize to the vegetal/dorsal pole
- stabilizing nuclear β-catenin in the dorsal region
- induces the organizer to secrete Nodal, Noggin, and Chordin
- specify the neuroectoderm and create the AP axis
BMP antagonists secreted by the notochord inhibit BMP signaling in the overlying ectoderm, promoting the formation of neuroectoderm instead of epidermis and thus leading to neural plate formation.
What is the function of the notochord in neurulation?
signalling centre - secreted BMP antagonists, induces overlying ectoderm to become neuroectoderm
- releases Shh to pattern ventral NT
How does neural induction occur in mice embryos?
In mice, the DVE and AVE (anterior visceral endoderm) regions secrete Lefty1 and Dkk1, inhibiting Nodal and Wnt signalling at the anterior, while promoting these signals in the posterior. This establishes the posterior primitive streak and the AP axis, leading to neural induction.
signals:
- Nodal and Wnt signalling in the posterior region promote primitive streak formation
- Lefty1 and Dkk1 inhibit these signals at the anterior
ensures proper axis formation and neural induction
conservation of BMP antagonism specifying neuroectoderm in ectodermal plate
- BMP antagonism promotes neuroectoderm fate from ectoderm – this mechanism is conserved across species:
Xenophus – organiser in dorsal part of embryo secretes Nodal & BMP antagonists (Noggin + Chordin)
- broad expression of BMP in ectoderm promoting epidermal fate blocked by antagonists in dorsal region
- neuroectoderm fate in dorsal region near organiser
mice – epiblast/future ectoderm contains regions that become neuroectoderm – BMP antagonist secreted by gastrula organiser at tip of primitive streak
- no BMP signalling at that region = neuroectodermal fate instead of epidermal
humans – primitive streak from posterior to anterior end, regresses & lays down notochord underneath neural plate/ ectoderm
- BMP antagonists secreted from notochord – signals to overlying ectoderm; induces neuroectoderm fate instead of epidermis
What are the key steps in neural tube formation during primary neurulation?
The edges of the neural plate elevate, forming folds.
These folds migrate toward each other and fuse at the dorsal midline.
The neural tube (NT) fully internalizes and detaches from the overlying ectoderm.
The NT then gives rise to the brain and spinal cord.
What are the closure points of the neural tube in humans?
closure point/neuropore 1 = boundary between hindbrain & SC (bidirectional closure)
closure point 2 = between forebrain & midbrain
closure point 3 = most rostral/ cranial end of neural plate (anterior neuropore)
closure point 4 = within hindbrain region
closure point 5 = at most caudal-end of NT/ tail-bud region (posterior neuropore)
What is primary neurulation?
primary neurulation = process where the neural plate shapes, folds, and closes to form the neural tube
- NT closure happens at specific points along AP axis
- ends with the closure of the cranial and caudal neuropores
- process gives rise to the brain and spinal cord
What is secondary neurulation, and where does it occur?
Secondary neurulation occurs in the tailbud region (most caudal end) of the embryo. Mesenchymal cells from the mesoderm and ectoderm condense to form a solid rod, which later hollows out to form a tube. This section of the neural tube fuses with the primary neural tube at the level of somites 30-31, forming the caudal-most part of the spinal cord.
Which pathway controls convergence-extension during neurulation?
The Wnt-PCP pathway (Planar Cell Polarity) controls convergence-extension. It involves Wnt signaling interacting with FZD receptors, activating Dishevelled, and regulating RHO GTPases, kinases, and downstream effectors (like Celsr, Scribble, Vangl2) that impact cell polarity, motility, and behavior.
Mutations in PCP components disrupt convergence-extension, leading to improper neural plate shaping. This can result in a broad, flat neural plate and failure in neural tube closure, causing neural tube defects such as craniorachischisis, where the entire neural tube remains open.
What is the role of cell wedging in neural plate folding?
Cell wedging via apical constriction is essential for forming hinge points, allowing the neural plate to fold. Neural plate cells change from columnar to bottle-shaped due to apical constriction, creating physical hinge points for neural plate bending. This process is regulated by the Wnt-PCP pathway.
Where do hinge points form along the AP axis of the neural tube?
In the brain, only the Median Hinge Point (MHP) is formed.
In the upper spine, MHP is also present.
In the intermediate spine, both MHP and Dorsolateral Hinge Points (DLHP) are formed.
In the lower spine, DLHPs are more prominent than MHP.
How is the formation of hinge points regionally controlled?
In the brain and upper spine, Shh signaling from the notochord suppresses Noggin (BMP antagonist), allowing BMP2 expression in the dorsal neural plate, promoting MHP formation.
In the lower spine, Shh signaling is low or absent, allowing Noggin to inhibit BMP2 signaling, enabling DLHP formation instead of MHP.
When do neural crest cells (NCCs) begin to migrate? How do neural crest cells contribute to neural tube closure?
NCCs are specified at the edges of the neural plate as the neural tube forms. Migration in the cranial/anterior region begins before neural tube closure is complete, while migration in the spinal/caudal/posterior region occurs after the neural tube has closed.
NCCs migrate from the edges of the neural plate during neurulation. Their early migration in the anterior neural tube is crucial for proper closure, particularly in the anterior region. In the posterior region, NCC migration happens after the neural tube closure is completed.
What mechanisms support neural tube closure?
Cell wedging via apical constriction: Neural plate cells become bottle-shaped, initiating hinge point formation.
Hinge point formation: MHP (high Shh) and DLHP (low Shh, Noggin suppresses BMP2).
PCP signaling: Controls convergence-extension and apical constriction.
NCC migration: Early in the anterior neural tube and after closure in the posterior.
Apoptosis: Programmed cell death in the anterior neural tube helps remodel the tissue and supports the fusion of neural folds.
