Neurulation Flashcards
What is the first major organ type created during development?
Central nervous system
What germ layer becomes the neural tube?
Ectoderm
What 3 signals are involved in the formation of the neural tube?
BMP, Noggin, Shh
What is the sequence of events that forms the neural tube?
- Neural epithelial cells expand to form neural plate
- Neural plate bends at medial hinge point
- Dorsolateral hinge points form and the folds converge inwards
- Folds connect and tube closes
- Neural tube pulls away from the epidermal ectoderm and the neural crest cells delaminate and migrate
What is primary neurulation?
The formation of a tube by bending a sheet of cells into a tube
What is secondary neurulation?
Neuromesodermal cells form a rod that gets hollowed out to form a tube
What are the 2 hinge points in the neural tube?
Medial and dorsolateral
What causes the hinge points to form? What signals are involved?
Apical constriction. A medium amount of BMP is required to form the hinge points
What happens to the hinge points if there is too much BMP?
No hinge points form. BMP inhibits the apical constriction
What happens to the hinge points if there is too little BMP?
The apical constriction happens sooner than its supposed to, and forms an exaggerated hinge point
Where does Shh in the neural tube originally come from?
The notochord
How does Noggin interact with BMP and Shh in the neural tube?
Noggin inhibits BMP, and Shh inhibits Noggin
What mechanism closes the neural tube?
Zipper
How do the two sides of the neural tube contact each other during closure?
Filopodial bridges and cadherins
How does the zipper work?
Actin filaments just ahead of the zipper contract, which creates a pull anterior of the zipper. The pull then causes resistance in the cells posterior to the zipper, and reduction of the posterior resistance pushes the zipper anterior to close the neural tube
How does the neural tube become separated from the epidermal ectoderm above it?
Differential cell adhesion, cadherins, and neural crest cell delamination
How do cadherins play a role in the separation of the neural tube from the overlying ectoderm?
The neural tube cells express N-cadherin and the ectoderm expresses E-cadherin. The cells will associate with other cells expressing the same cadherin
What are the 3 mechanisms that could cause anencephaly?
- Problems with cell polarity
- Problems with cell adhesion
- Problems with morphogen signalling
Problems in what type of neurulation causes anencephaly?
Primary
Problems in what type of neurulation causes spina bifida?
Secondary
What two axes does the neural tube differentiate on?
Anterior-posterior and dorsal-ventral
What features are created by anterior-posterior differentiation in the neural tube?
Brain in the anterior end, spinal cord in the posterior end
What features are created by dorsal-ventral differentiation in the neural tube?
A variety of nerve types that create different functional units
What is the first step in creating a brain?
Swelling in the anterior end of the neural tube
What causes the swelling of the anterior neural tube?
Occlusion from the closure of the neural tube lumen in the posterior end, which forces the fluid into the anterior end and causes it to swell
What are the 3 vesicles in the tripartite brain?
Prosencephalon, mesencephalon, rhombencephalon
What are the 3 vesicles in the pentapartite brain?
Telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon
What happens to prosencephalon when the brain becomes more differentiated into a pentapartite brain?
Splits into the telencephalon and diencephalon
What happens to mesencephalon when the brain becomes more differentiated into a pentapartite brain?
Stays as the mesencephalon
What happens to rhombencephalon when the brain becomes more differentiated into a pentapartite brain?
Splits into the metencephalon and the myelencephalon
Where does the telencephalon come from?
The prosencephalon
Where does the diencephalon come from?
The prosencephalon
Where does the metencephalon come from?
The rhombencephalon
Where does the mylencephalon come from?
The rhombencephalon
How does dorsal-ventral differentiation create a functional circuit in the vertebrate spinal cord?
Dorsal side gets directed to form sensory neurons, and the ventral part forms motor neurons. Middle regions form interneurons
Which two signal gradients cause dorsal-ventral differentiation of the neural tube? Where are the signals coming from?
Shh from the notochord and floor plate, and BMP from the epidermis and roof plate
Which two transcription factors get produced by the roof plate when it receives the BMP signal? What signalling pathway are they part of?
Activin and dorsalin. Part of the TGF-beta pathway
What happens if we transplant notochord cells near another part of the neural tube?
It induces a second floor plate and a second set of motor neurons
What type of cells are in the early embryo neural tube, before they become differentiated?
Neural stem cells/neuroblasts
What are the 2 cell types neuroblasts can become?
Ventricular cells or radial glial cells
What do ventricular cells do?
They remain in the centre of the neural tube and secrete cerebrospinal fluid
Can radial glial cells differentiate further? What can they become?
Yes, they retain multipotency. They can become neurons or glial cells
What are the 4 types of glial cells?
Oligodendrocytes, Schwann cells, microglia, astrocytes
What do oligodendrocytes and Schwann cells do?
Wrap and insulate neuron axons and increase the speed of signal transmission
What do astrocytes do?
Regulate metabolites, ion balance, cell structure and repair
What do microglia do?
Immune cells of the CNS
Which way in the neural tube do cells go as they progress through the cell cycle?
Towards the basal surface
What happens to the neural tube as cells progress through the cell cycle and move outwards?
It expands
What are the 3 zones of the neural tube?
Ventricular zone, intermediate zone, marginal zone
What type of cells are in the ventricular zone?
Neuroblasts
What type of cells are in the intermediate zone?
Radial glial cells and neurons
What type of cells are in the marginal zone?
Contains the axons and dendrites of neurons
Which two zones of the neural tube are expanding?
Intermediate and marginal. Ventricular zone stays the same size
What are the two types of cell division undergone by radial glial cells during the expansion of the neural tube?
Symmetrical: radial glial cell divide into two radial glial cells, which increases the population
Asymmetrical: radial glial cell divides into a neural progenitor cell and a radial glial cell
How is the cerebrum organized?
Migrating radial glial cells form 6 stacks and >40 sheets of cells, each with a different function
Where do the neural progenitor cells go?
They migrate through the intermediate zone and form the cortical plate
How do the neural progenitor cells know when to stop migrating?
Reelin signalling
What does Reelin do?
Causes actin filament breakdown and immobilizes the cell
Where is Reelin coming from?
Released by cells on the basal surface
What is the receptor for Reelin?
Disabled-1
What happens to cells receiving very little Reelin signal?
They keep moving
What happens to cells receiving a moderate amount of Reelin signal?
Activates Disabled-1 and activates N-cadherins and stabilizes actin. Promotes filopodial extensions along the integrin-fibronectin pathways towards region with high N-cadherin expression
