References

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References
Wolpert Chapter 11, 375-380 and 381-382 (dont
need to know about asymmetric divisions and the
peripheral nervous system) DB Web
site http//www.lifesci.sussex.ac.uk/teaching/bio
logy/cws/dvb/index.htm
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Origin of Drosophila nervous system
Drosophila fate map
Mesodermal invagination
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Proneural clusters

• Achaete expression in PNCs of the neurogenic
  ectoderm of Drosophila
• Achaete is part of a gene complex called the
  Achaete-Scute complex (AS-C)
• Genes of the AS-C are called pro-neural genes
  because they promote a neural fate

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Specification of cell identity in the nervous
system

• Neurons in Drosophila arise from proneural
  clusters.
• The neurogenic zone or neurectoderm, consisting
  of cells that can become either neural cells or
  epidermis, form on either side of the ventral
  mesoderm in the early embryo.
• Proneural gene expression, such as the
  transcription factor genes of the achaete-scute
  complex gives the potential to become neural
  precursors.
• This complex encodes a number of basic
  helix-loop-helix transcription factors that form
  homodimers and heterodimers that bind to genes
  which initiate neural specification.

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Lateral Inhibition

• One cell in the cluster starts to express
  pro-neural genes at higher levels
• This cell will become the neuroblast
• The cell that becomes a neuroblast produces a
  signal that prevents its neighbours from becoming
  neuroblasts
• This is a process known as lateral inhibition

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Notch signalling
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Cell identity and lateral inhibition

• Lateral inhibition allocates neuronal precursors.
  
• One cell becomes the neural cell while lateral
  inhibition prevents surrounding cells from doing
  so.
• When Delta (the ligand) and Notch (the receptor)
  interact, activation of Notch leads to inhibition
  of the proneural genes and shutting down of that
  program.
• Initially all cells of the cluster express both
  Notch and Delta but one cell wins out (by
  expressing more Delta).

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The Notch-Delta signaling pathway mediates
lateral inhibition
Activation of N by Dl leads to down-regulation of
AS-C genes in the N cell Dl is activated by AS-C
so inhibition of AS-C by N signalling leads to
down-regulation of Dl Therefore, in the N
(reception) cell, Dl will be down-regulated. In
the Dl (signalling) cell, Dl will be
up-regulated This is a feedback loop
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The neuroblast is singled out by a random
processes
Initially, all cells in the pro-neural cluster
express N and Dl One cell gains an advantage, for
example, by expressing Dl sooner or at higher
levels Through interacting with the N receptors
on its neighbours, it inhibits their further
neural development and also suppresses their
production of Dl Initially equivalent cells are
resolved by lateral inhibition into neural
precursor and others (epidermal)
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The vertebrate nervous system is derived from the
neural plate
The neural tube forms by folding of the neural
plate. It sinks beneath the surface and is
overlain by the epidermis The neural tube gives
rise to the brain and the spinal cord Neural
crest cells migrate away from the neural tube to
form the sensory and autonomic nervous system
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Lateral inhibition specifies single cells as
neuronal precursors in the vertebrate nervous
system
In vertebrates, expression of the neurogenin gene
is required for neuronal differentiation Neurogeni
n is a transcription factor, distantly related to
the AS-C genes
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The vertebrate nervous system

• Most of the vertebrate CNS comes from the neural
  plate.
• In addition sensory placodes in the head region
  give rise to the cranial nerves.
• Specification of vertebrate neuronal precursors
  also involves lateral inhibition.
• Delta activates Notch which inhibits synthesis of
  neurogenin (related to the achaete-scute
  proteins).
• The cell expressing neurogenin then expresses
  neuroD (a transcription factor required for
  neuronal differentiation).

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Cut and paste experiments originally by
Horstadius
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Sea Urchin development
In the sea urchin cut and paste experiments
indicate that cytoplasmic factors are localised
in the egg (Robs lectures) Cell differences
arise through inheritance of these differences
and cell-cell interactions. Many animals use
both these mechanisms to specify cell differences.
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Conclusions

• the sea urchin has an animal-vegetal polarity
  established before fertilisation.
• animal and vegetal half embryos develop
  differently, neither producing normal embryos.
• the fate of the micromeres to be skeleton is
  determined early in development, but other cells
  are specified more slowly.
• the considerable capacity for regulation reflects
  the importance of cell-cell interactions in
  establishing cell fate.
• cell autonomous nuclear accumulation of
  beta-catenin is necessary for skeleton formation
  and appears to trigger Delta-Notch signaling to
  establish secondary mesenchyme derivatives
  (muscle and pigment cells).

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From Wolpert, chapter 3
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Model for the action of the organiser
BMP4 (and other molecules) is a powerful
ventralising factor Organiser proteins such as
noggin chordin block BMP4 The effects of BMP4
and its antagonists can be seen in all 3 germ
layers BMP4 may elicit the activation of genes in
a concentration-dependent manner
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• Nieuwkoop centre formed in the blastula.
• Cells of the Nieuwkoop Centre contribute to
  endoderm
• The Spemanns Organiser forms just above the
  Nieuwkoop Centre during late blasula, early
  gastrula
• Cells of the Organiser contribute to dorsal
  mesodermal derivatives
• Blastula transplantation experiments explained
  by induction of Organiser

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