Development of the vertebral column

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Development of the vertebral column
Claudio D Stern Department of Anatomy
Developmental Biology University College
London c.stern_at_ucl.ac.uk http//sternlab.anat.
ucl.ac.uk
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Segmentation of the nervous system and skeleton
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Somite formation progresses from head to tail
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Embryo
R
R
R
R
C
C
C
C
notochord
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Model 1 Resegmentation the classical view
(Remak, 1855)
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Model 2 1 somite gt 1 vertebra
We still dont really know the answer for sure
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How do the vertebrae (somites) and nerves relate
to one another? the textbook view
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How do the vertebrae (somites) and nerves relate
to one another? take a look
Motor nerves (and sensory) only in rostral half
of somite!
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Is this a property of the nervous system, or of
the somites?
Neural tube rotation
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How do rostral and caudal half cells interact?
Multiple-rostral somites
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How do rostral and caudal half cells interact?
Multiple-caudal somites
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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?
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When is the decision to segment made? Try
heat-shock
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Heat-shock produces not one, but multiple,
repeated anomalies, 7-somites apart!
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Since 1 pair of somites forms every 90 minutes, 7
somites 10 hours
What process could be 10 hours long? The
cell cycle?
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Cell cycle synchrony for cells that segment
together
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Synchrony can even by seen directly looking at
mitoses
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A cell cycle model for segmentation
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Another clock (oscillator) Notch signalling
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Expression of chick Hairy-1 oscillates in
presomitic mesoderm
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But we still dont 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.
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What makes cells become somites in the first
place?
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Movement of Hensens node cells into notochord
Anterior primitive streak cells give rise to
somites
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Fate map of the primitive streak
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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 dont know how the two are
coordinated.
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The molecular basis of neural segmentation Peanut
agglutinin binding to the caudal half
somite (peanut agglutinin recognises a
carbohydrate structure attached to proteins)
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Assay for inhibition of axon growth the
collapse assay
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Assay for inhibition of axon growth the
collapse assay
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An extract from sclerotome causes axon collapse
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Peanut agglutinin chromatography removes the
collapsing activity PNA recognises 2 protein
bands 48 and 55 kDa.