Lecture 3 - Developmental Neurobiology - Neurulation

what happens in neurulation?

the neural plate forms into the neural tube

• neural plate grows and elongates along the A-P (anterior-posterior) axis

• the lateral edges of the neural plate roll up and fuse, giving rise to the neural tube

how is neurulation observed?

observed morphologically or through observing expression of Sox2 (marker of neural stem cells)

what drives neurulation?

gastrulation

what is gastrulation?

• the process which transforms the embryo from a one-dimensional layer of cells to a multi-layered embryo

• during gastrulation, the germ layers assume their final positions and axes become obvious

what is gastrulation driven by?

changes in cell behaviour of organiser cells

what does the organiser region express?

BMP antagonists

• they are secreted from the organiser, they get out and diffuse and inhibit BMP, these cells become neural

what else do organiser cells express?

• a pile of special master transcription factors called siamois and goosecoid

• they are master regulators of organiser identity

what are siamois and goosecoid?

• master regulators of organiser identity

• they transcriptionally activate many genes - which encode factors that act intrinsically within organiser cells

what is meant by master regulators of organiser identity?

• transcriptional factors that act in a cell autonomous manner, act within the organiser cell

what do siamois and goosecoid do once they are expressed?

they go back into the nucleus to turn on/off the expression of a whole set of genes

what do siamois and goosecoid do?

• they activate a number of genes that act intrinsically within the organiser cells

• cell intrinsic manner (direct next steps)

what happens to the cells once siamois and goosecoid activate the genes that act intrinsically within the organiser cells?

cells differentiate and undergo convergent extension

what is convergent extension?

• a group of cells trying to converge together, meaning come together but they have nowhere to go

  • so instead, they will interpolate with each other and extend in a line (in a different arrangement - no cells lost or dead)

what is the specific order of the organiser cells that undergo convergent extension?

1. the first cells that extend forward and anteriorly are the anterior mesoderm cells

2. followed by the pre-chordal mesoderm cells

3. followed by the chordamesoderm cells

   —> they all go inside and give rise to the rod in this order

what is the process of neural tissue giving rise to the long thin rod of cells? (step by step)

1. organiser cells differentiate into axial mesoderm (chordamesoderm)

2. they involute (curve) and intercalate

3. undergo conversion extension

4. move inside under midline

5. forming a long thin rod of cells (beneath the midline of induced neural plate)

what is the name of the long rod and what are the 2 main parts it is composed of?

• axial mesoderm

• composed of prechordal mesoderm and notochord

what are the types of cell movement that occur during gsatrulation?

1. invagination

2. ingression

3. involution

4. epiboly

5. intercalation

6. convergent extension

invagination

a sheet of cells (epithelial sheet) bend inwards

ingression

cells leave epithelial sheet and become freely migrating mesenchyme cells

epiboly

a sheet of cells spreads by thinning

intercalation

a row of cells move between one another - creating a longer but thinner array of cells

convergent extension

rows of cells intercalate but it is highly directional

what is the axial mesoderm composed of?

• notochord (hindbrain/spinal cord)

• prechordal mesoderm (forebrain)

what does involution mean?

turning inside

key information of notochord:

• lies underneath the neural tube

• not a part of the neural tube

• has differentiated from mesoderm organiser cells

what do the forces of convergent extension drive?

the elongation of cells in the adjacent layer in the neural plate

• responsible for elongation and transition of neural plate cells to neural tube cells

• this force is partly responsible for neurulation

what happens to the embryo during gastrulation?

• shape of embryo undergoes a significant change

• goes into anterior posterior axis

what do the mesoderm cells do?

continue to instruct neural cells to tell them what neural tissue they will be

where is the prechordal mesoderm and what does it instruct?

• underlies anterior parts of axis

• instructs overlying neural cells to become brain

what does the notochord instruct?

• instructs overlying neural cells to become posterior neural cells - hindbrain and spinal cord

neurulation is not only driven by mechanical forces but also what?

• intrinsic changes that drive changes in cell shape

what is the arrangement of cells of a neural plate?

columnar epithelium

what is the shape of the forming neural tube?

triangular

where are neuroepithelial cells polarised?

along the apical versus basal part of the cells

what happens if the band of F-actin pulls tight?

• band of f-actin at apical membrane - pulled tight

• the cells are constricted at the edge and so the shape changes

• this is how neurulation is driven by changes in cell shape