positional information: fields, boundaries, and gradients
DESCRIPTION
Positional information: fields, boundaries, and gradients. Development requires a dramatic increase in the amount of information contained within the organism. The "new" information is contained in the genome, and is gradually translated into cellular processes. - PowerPoint PPT PresentationTRANSCRIPT
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Positional information: fields, boundaries, and gradients
Development requires a dramatic increase in the amount of information contained within the organism.
The "new" information is contained in the genome, and is gradually translated into cellular processes.
The principal ways in which this happens is by (1) subdivision of larger fields of cells into smaller fields, and (2) specifying the "address" of each cell within the field.
This is a recursive process that requires translation of gradients of gene expression into sharp boundaries, and initiation of new gradients by these boundaries
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Specification of cell fates
Positional cues (Pattern formation):
Cell fate is determined by its spatial position within a morphogenetic field during a critical time period
Historical cues (Cell lineage):
Cell fate is determined by inherited molecules or gene expression states
Both mechanisms are required for cell specification, and often act simultaneously.
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Pattern formationY
X
Cell fate
Cue 1
Cue 2
Morphogenetic (progenitor) field is a region or a group of cells that show no overt differentiation, but that is “destined” to give rise to a particular organ or structure. Morphogenetic fields are to some extent autonomous and integrated.
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Primary and secondary fields
Y
X
etc.
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Morphogen gradients
A morphogen is a (usually) secreted molecule that induces cell fate decisions in recipient cells in a concentration-dependent manner
Requires:Spatially restricted productionLong-range distribution (passive or active)Reception and interpretation
Interpretation is context-dependent
Most animal morphogens belong to a small number of well-conserved and widely distributed families
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Morphogen gradient
Source
Position
Con
cent
ratio
n
Positional information
Positional information may include both scalar and vector components (distance and direction)
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Gradients and cell polarity
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Wolpert's "French flag" model
Single gradient
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Wolpert's "French flag" model
Double gradient
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Signal transduction
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Positional information is translated into the activation and repression of target genes
Responses to morphogen gradients: activation / repression of target genes; cell proliferation and growth; morphogenetic movements
Responses are context-specific
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Translating boundary into gradient
hh
en
Hh
ptcsmo
ci
dpp
cici
Boundary of Engrailed expression serves as the source of Hedgehog gradient
Hedgehog activates expression of a second morphogen, Dpp, which establishes a bidirectional gradient
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Translating gradient into boundary
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Threshold responses to the Dorsal morphogen gradient
sna
sog
zen
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Threshold responses to the Dpp morphogen gradient
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Threshold responses to the Dpp morphogen gradient
(Lost in dpp / - )
hnt ush
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msh
ind
vnd
After the gradient: Refining position-specific cell fates
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Cowden and Levine 2003
After the gradient: Refining position-specific cell fates
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Short-range (contact-mediated) signaling
Notch signaling
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Sensory organ precursor lineage in Drosophila
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Interplay of position and lineage
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Context-dependent action of morphogen gradients
Anterior-posterior Dorso-ventral
Same morphogen, different targets, different responses
sna
sog
zen
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"Selector genes" provide the context in which positional information is interpreted
Act as digital switches that “toggle” between distinct fatesCan be induced by morphogens or other selector genesForm multi-layer hierarchies
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Distal-less
Dpp
EGFR
Wg
Target genes,including other
selectors and signals
Signaling pathways activate selector genes…… and vice versa
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Types of selector genes
Organ Spatial region
Cell / tissue type
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HOX genes and axial patterning
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Combinatorial specification of cell fates
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Combinatorial control of cell fates
Signal 1 Signal 2Selector A Selector B
Target Gene X Target Gene Y Target Gene Z
Cell fate Cell fate Cell fate
A relatively small “toolkit” of signals and selector genes can specify a wide range of cell fates by a combinatorial mechanism
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Control of gene expression by selector genes and signaling pathways
Different signal/selector combinationsdefine different cell fates and geneexpression domains
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Precise spatial control of cell fates
Culi and Modolell 1998
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Precise spatial control of cell fates
Garcia-Garcia et al 1999
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Precise spatial control of cell fates
Renaud and Simpson 2002
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Combinatorial control by overlapping selectors
Selector A
Selector B
Selector C
Cell fate1 Cell fate
2Cell fate3
Cell fate4
Cell fate5
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Axial patterning by overlapping regional determinants
Multiple positions along the Proximo-Distal axis are defined by selector genes expressed in overlapping concentric domains
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Axial patterning by overlapping regional determinants
Kojima 2004
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Progressive regionalization of morphogenetic fields
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Combinations of regional identities establish new regional identities
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Regulatory hierarchies in development
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Genes and molecules that control animal development are widely conserved
Signaling pathways
Hedgehog NotchDpp/ TGFRas/ rafWingless/ Wnt Jak/ Stat
Selector genes
HOX geneseyeless/ Pax6 (eye development)Distal-less (appendages)tinman (heart)