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 Presentation
nal information: fields, boundaries, and gr 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
Transcript
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
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.
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.
Primary and secondary fields
Y
X
etc.
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
Morphogen gradient
Source
Position
Con
cent
ratio
n
Positional information
Positional information may include both scalar and vector components (distance and direction)
Gradients and cell polarity
Wolpert's "French flag" model
Single gradient
Wolpert's "French flag" model
Double gradient
Signal transduction
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
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
Translating gradient into boundary
Threshold responses to the Dorsal morphogen gradient
sna
sog
zen
Threshold responses to the Dpp morphogen gradient
Threshold responses to the Dpp morphogen gradient
(Lost in dpp / - )
hnt ush
msh
ind
vnd
After the gradient: Refining position-specific cell fates
Cowden and Levine 2003
After the gradient: Refining position-specific cell fates
Short-range (contact-mediated) signaling
Notch signaling
Sensory organ precursor lineage in Drosophila
Interplay of position and lineage
Context-dependent action of morphogen gradients
Anterior-posterior Dorso-ventral
Same morphogen, different targets, different responses
sna
sog
zen
"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
Distal-less
Dpp
EGFR
Wg
Target genes,including other
selectors and signals
Signaling pathways activate selector genes…… and vice versa
Types of selector genes
Organ Spatial region
Cell / tissue type
HOX genes and axial patterning
Combinatorial specification of cell fates
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
Control of gene expression by selector genes and signaling pathways
Different signal/selector combinationsdefine different cell fates and geneexpression domains
Precise spatial control of cell fates
Culi and Modolell 1998
Precise spatial control of cell fates
Garcia-Garcia et al 1999
Precise spatial control of cell fates
Renaud and Simpson 2002
Combinatorial control by overlapping selectors
Selector A
Selector B
Selector C
Cell fate1 Cell fate
2Cell fate3
Cell fate4
Cell fate5
Axial patterning by overlapping regional determinants
Multiple positions along the Proximo-Distal axis are defined by selector genes expressed in overlapping concentric domains
Axial patterning by overlapping regional determinants
Kojima 2004
Progressive regionalization of morphogenetic fields
Combinations of regional identities establish new regional identities
Regulatory hierarchies in development
Genes and molecules that control animal development are widely conserved
Signaling pathways
Hedgehog NotchDpp/ TGFRas/ rafWingless/ Wnt Jak/ Stat
