Pattern formation

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Pattern Formation
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Morphallaxis
Remodeling of tissue into a whole new organism
No new cell division
Hydra
Fig. 18.25, pg. 580
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Epimorphosis
Addition of a part to the whole New growth
and cell division
Salamander
Fig. 18.19, pg. 574
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Proposed Mechanisms for Pattern Formation

• Morphogen Gradient

• Haptotaxis Induction of cell growth

• Thermodynamic (Temporal) Model

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Limb Field
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Blastema
Regeneration
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Fig. 16.3, pg. 507
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Dorsal
Posterior
Distal
Proximal
Anterior
Ventral
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Limb Outgrowth
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Differential Control of 3 Axes
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Chick Wing
Fig. 16.1, pg. 506
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Wing
Fibroblast Growth Factor FGFs 12 genes with
100s of protein isoforms
Fig. 16.9, pg. 511
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Wing
Fibroblast Growth Factor FGFs 12 genes with
100s of protein isoforms
Fig. 16.9, pg. 511
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FGF10 stabilized regionally by Wnt8c and Wnt2b
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Fig. 16.19, pg. 519
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Homeotic Hox genes Genes which regulate body
segmentation and proximal / distal differentiation
Similar to Fig. 16.14, pg. 515
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Characteristics of Hox genes

• Mice and humans have 4 Hox clusters (a total
  of 39 genes
• in humans) located on 4 different
  chromosomes.

• In humans HOXA, HOXB, HOXC, HOXD

• Act along the developing embryo in the same
  sequence that they
• occupy on the chromosome.

• All genes in the mammalian Hox clusters show
  some sequence
• homology to each other (especially in their
  homeobox) but very
• strong sequence homology to the equivalent
  genes in Drosophila.
• HoxB7 differs from Antp at only two amino
  acids, HoxB6 at four.

- mouse HoxB6 gene inserted in Drosophila can
substitute for Antennapedia producing
legs in place of antennae
Conclusion?
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Selector genes have retained, through millions of
years of evolution, function of assigning
particular positions in the embryo. The
structures actually built depend on a different
set of genes specific for a particular species.
Genetic Specificity
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Humerus
Radius
Radius
Ulna
Ulna
Humerus
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X-irradiate
Remove bud and transplant to non-irradiated host
Limb Bud
Result ?
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Thalidomide exposure between D20 D36 of
pregnancy
Phocomelia
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Fig. 16.13, pg. 514
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Posterior
Distal
Proximal
Anterior
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Anterior
Retinoic Acid
ZPA
Posterior
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III
Chick Wing
Fig. 16.1, pg. 506
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4
3
2
2
Results of Graft I
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4
2
3
4
4
3
Results of Graft II
4
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Experimental Design - ZPA
from hamster transplanted to chick limb bud
Possible Results ?
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Fig. 16.18, pg. 518
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Fig. 16.19, pg. 519
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Sonic hedgehog (Shh) is the active agent
Fig. 16.16, pg. 516
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Gene receptors for morphogen enhancer
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Possible models of ZPA activity
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Fig. 16.20, pg. 520
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Fig. 16.21, pg. 521
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Dorsal / Ventral Axis Determination
Wnt7a
Lmx1b
En1 transcription factor represses Wnt7a
expression in ventral ectoderm
Wnt7a deficient mice --- Duplication
of ventral tendons and footpads
Fig. 16.22, pg. 521
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Summary of proposed events in limb formation
Fgf-10
Induction
Maintenance
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Maintenance of Shh in dorsal ectoderm
Shh blocks cleavage of GLi3 to GLi3R creating a
gradient of GLi activator and GLi3 repressor
Gremlin blocks BMPs which inhibit FGFs
Fig. 16.23, pg. 522
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Aptosis - Programmed cell death
Noggin protein expressed
No expression of BMP4 Due to Noggin expression
Expression of BMP4
Fig. 16.24, pg. 522
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BMP class of genes first identified as genes
that stimulate bone formation - Bone
Morphogenetic Proteins -
BMPs now shown to induce chondrogenesis and
aptosis
Context Dependency - Response depends on
the age of the target cells
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Trematode cysts developing in limb
bud field