SBS 306 Lecture 13 SOFT TISSUE FORMATION

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SBS 306 Lecture 13SOFT TISSUE FORMATION
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Summing up the last lecture

• In the last lecture we say that
• 1) The chick embryo start as a flat sheets of
  cells
• 2) In the centre of this a slit develops, the
  primitive streak and cells migrate in to form
  mesoderm and endoderm
• 3) A node forms near the prospective anterior
  end. The area anterior to the node will become
  the head
• 4) The node moves backwards. As the node passes
  the underlying cells become committed to a
  particular position along the body axis. This is
  marked by expression of combinations of Hox
  genes. The head develops separately
• 4) Movements which we did not discuss lead to
  specification of the right and left side of the
  body

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Continued

• Although cells become specified as the node
  passes over, differentiation is delayed. However
  after a period the notochord differentiates and
  induces formation of somites in the mesoderm and
  neural plate in the ectoderm
• The neural plate folds in to form the neural tube
  Not all of the immigrating cells are incorporated
  in the tube, some remain and form the neural
  crest.
• The body rounds up forming the primitive gut
• The limbs develop as buds of mesenchyme coated
  with ectoderm. Secretion of FGF-4 from the
  apical ectodermal ridge drives development,
  diffusible factors provide information on the
  anterior and posterior and on the dorsal and
  ventral axes, the time of exit from the progress
  zone on the proximal distal axis.

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What was left out

• The digits are formed by death of the
  intermediate cells by apoptosis. This process
  also separates the bones of the lower arm and
  leg. The instruction, as usual, comes from
  mesoderm probably via BMP-4
• We will not discuss formation of the heart and of
  the vasculature, development of the CNS or
  development of the extraembryonic membranes. I
  will just mention that the open gut of the flat
  early embryo is closed by rounding up.

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Differentiation of the somites

• As we have seen somites undergo further
  differentiation. Firstly the sclerotome, which
  will give rise to the cartilege and then the bone
  of the vertebral column and ribs separates from
  the dermomyotome which, in its turn breaks up
  with the cells of the dermotome migrating out to
  form the dermis. The myotome gives rise to the
  muscles of the back and, in the somites close to
  limb buds, to the muscles of the limbs

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Voortrekkers

• Limb muscles are formed from cells which have
  migrated from the somites in the region where the
  limb will form.

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Set forth

• Muscle development is associated with the
  expression of muscle regulatory factors assisted
  by muscle enhancing factor. Cells which will
  form the thoracic muscles express either MyoD or
  myf5, two muscle regulatory factors and cease to
  express pax-3 which becomes confined to the
  putative skeletal muscle cells
• A signal from the notochord/neural tube, probably
  BMP-30, loosens adhesions between the prospective
  limb muscle cells and causes them to bind
  hyaluronan. Pax-3 induces formation of the HGF
  receptor c-met.

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Set forth

• Mesenchymal cells in the limb bud synthesise HGF.
  This diffuses out from the limb bud and acts as
  a chemotactic factor. The muscle cells migrate
  in to the limb.
• Once in the limb the muscle cells assemble into
  blocks and express myf-5.
• As the limb matures the muscle blocks break up
  and form the individual muscles. myogenin and
  MEF2 are now expressed and commence the process
  of fusing the majority of myocytes to form muscle
  fibres
• Until the last stage of fusion myocytes can be
  transplanted. The positional information comes
  from mesodermal cells

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Neural crest cells have form a range of tissues

• But we will keep things simple and not go into
  most of the interactions

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More migrants

• Cells from the neural crest migrate over the
  somites forming pigment cells, the dorsal root
  and sympathetic ganglia and the other tissues
  shown in an earlier slide. Some emigrate to form
  the adrenal medulla

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Formation of the adrenal glands

• The adrenal glands consist of two distinct areas.
  The cortex differentiates first from mesenchymal
  tissue and begins to secrete corticosteroids.These
  stimulate precursor cells which have emigrated
  from the neural crest to form the adrenal
  medulla. If, on the other hand, the same
  precursor cells are stimulated by fibroblast
  growth factor and nerve growth factor they
  differentiate into adrenergic sympathetic neurones

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Interactions between social cells

• The formation of the adrenal medulla is not the
  only example of interactions between cells
• The differentiation of neural crest cells seems
  to be determined by interactions with their
  neighbours
• Formation of the dorsal root ganglia requires a
  factor called brain-derived neurotropic factor
  secreted by the neural tube
• Differentiation of melanocytes demands that a
  growth factor made by fibroblasts and
  keratinocytes binds to a receptor on the
  pre-melanocyte called kit. Mutations in either
  receptor or ligand result in albinism

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And the Kidneys

• The formation of the kidenys is especially
  complex as 3 distinct excretory organs develop.
  The development of the final forms depends on an
  interaction between bud on a duct formed earlier
  during development with mesenchyme

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Nerve cells like muscle grow into the developing
limb bud
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Orienteering

• The neurons put out long extensions, the axons
  which migrate as discussed earlier

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Orienteering

• In many cases the axons do not grow directly to
  their target but instead navigate using
  guideposts, cells which secrete a chemoattractant

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Control of migration
Migration of nerve axons involves both positive
and negative factors and both diffusible and
matrix-bound factors
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Development of the Internal Organs

• Lacrimal and salivary glands are formed as paired
  outbuddings from the primitive gut. The thyroid
  gland forms in a similar way but the cells
  connecting it to the gut die, probably by
  apoptosis, leaving the gland isolated. The
  thymus forms in a similar fashion but here the
  interior loses almost all traces of its
  epithelial origin. Lungs, liver and pancreas
  also form as paired outbuddings but in the latter
  two cases the buds fuse to form a single
  structure

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Development of the Lungs

• The lungs form as buds from the primitive gut.
  The then bud elongates it encounters
  bronchi-specifying mesoderm. This induces
  branching resulting in formation of the bronchial
  tree. The proximal section of the bud develops
  into the trachea.
• The message specifying a single tube or branching
  is specified by the surrounding mesoderm.
  Transplantation of mesoderm from the bronchial
  zone to around the trachea induces branching.
• EGF appears to be the most important factor, it
  induces branching on its own

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Continued

• Patterning of the developing bronchi is guided by
  positive growth factors such as EGF and PDGF
  which stimulate epithelial growth and negative
  growth factors such as TGF-beta which inhibits
  epithelial cell division but stimulates
  mesenchymal proliferation
• Alveoli form late in gestation (in humans at
  about 2 months). Differentiation is accelerated
  by corticosteroids and thyroxine-the former
  apparently by inducing mesenchymal cells to form
  fibroblast pneumocyte factor
• Interactions between FGF10 and Shh mediate
  branching

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Summing Up - General principles of development

• In many cases patterning reflects the effects of
  a three dimensional gradient of diffusible growth
  factors.
• The effects of these upon cells is to induce the
  synthesis of transcription factors. These
  include homeobox genes (hox, pax etc.) The
  effects of combinations of these define the cells
  position in the body.
• In higher animals one of the positional signals
  may come not from a diffusible factor but from
  the time taken for an organiser region to reach a
  particular site

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Continued

• Normally signalling is by secreted growth factors
  which bind to receptors on the target cells after
  which the signal is transduced to the nucleus.
  Insects can get round this by develping as a
  syncytium where the nuclear transcription factors
  can act ditrectly.
• Controlled migration of cells plays an important
  role at all stages of development. Signalling is
  by diffusible factors, interactions with other
  cells and interaction with the substrate
• Either ectodermal or mesodermal tissue can give
  instruction. Endoderm is generally patterned by
  mesoderm