Development of the vertebral column - UCL

Development of the vertebral column
Claudio D Stern
Department of Anatomy & Developmental Biology
University College London
c.stern@ucl.ac.uk
http://sternlab.anat.ucl.ac.uk

Segmentation of the nervous system and skeleton

Somite formation progresses from head to tail

Embryo:
C
R
C
R
C
R
C
R
notochord
Adult:
muscle
muscle muscle muscle
vertebra
vertebra
vertebra

Model 1: parasegmental relationship
(Neugliederung – resegmentation)
Model 2: segmental relationship
1 somite => 1 vertebra

Model 1: Resegmentation – the classical view
(Remak, 1855)

Model 2: 1 somite => 1 vertebra
We still don’t really know the answer for sure…

How do the vertebrae (somites) and nerves relate to one another?
… the textbook view

How do the vertebrae (somites) and nerves relate to one another?
take a look …
Motor nerves (and sensory) only in rostral half of somite!

Is this a property of the nervous system, or of the somites?
Neural tube
rotation
Somite
mesoderm
rotation

How do rostral and caudal half cells interact?
Multiple-rostral
somites

How do rostral and caudal half cells interact?
Multiple-caudal
somites

Tentative rule:
Whenever “like” cells are adjacent, they mix. Unlike cells
generate a border.
… but then there should also be a border in the middle of each somite?
“von Ebner’s fissure”

When is the decision to segment made? Try heat-shock…

Heat-shock produces not one, but multiple,
repeated anomalies, 7-somites apart!

Since 1 pair of somites forms every 90 minutes, 7 somites ~ 10 hours
What process could be 10 hours long? The cell cycle?

Cell cycle synchrony for cells that segment together…

Synchrony can even by seen directly – looking at mitoses:

A cell cycle model for segmentation

Another clock (oscillator): Notch signalling

Expression of chick Hairy-1 oscillates in presomitic mesoderm

But we still don’t know whether the Notch oscillator plays
a direct role in regulating either the timing of segmentation
or the size of somites.
Another hypothesis is that it is involved in regulating the
alternation between rostral and caudal sclerotome properties.

What makes cells become somites in the first place?

Movement of Hensen’s node cells into notochord
Anterior primitive streak cells give rise to somites

Fate map of the primitive streak

Conclusions:
BMP signalling (inhibited by Noggin) regulates the decision between
somitic and lateral plate mesoderm.
It is possible to induce somites to form that do not have rostrocaudal
polarity – therefore the decision to segment is regulated
independently from the decision to become rostral or caudal half.
The most parsimonious explanation at the moment is that Notch/Hairy
signalling regulates Rostral/Caudal properties, and something like
the cell cycle model regulates somite size and timing.
If so, we don’t know how the two are coordinated.

The molecular basis of neural segmentation
Peanut agglutinin binding to the caudal half somite
(peanut agglutinin recognises a carbohydrate structure attached
to proteins)

Assay for inhibition of axon growth: the “collapse assay”

Assay for inhibition of axon growth: the “collapse assay”

An extract from sclerotome
causes axon collapse

Peanut agglutinin chromatography removes the collapsing activity
PNA recognises 2 protein bands: 48 and 55 kDa.