Gradients and Tissue Patterning

Copyright
Contributors
Preface
Lighting up the central dogma for predictive developmental biology
Introduction
Turning the fruit fly Drosophila melanogaster into a substrate for predictive developmental biology
Lighting up the central dogma to assign quantitative and predictive meaning to arrows
Lighting up transcriptional dynamics
Lighting up protein dynamics and transcriptional input-output functions
Wiring up the synthetic embryo
Predicting the central dogma beyond transcription
Developmental programs as dynamical systems
Toward quantitative and predictive developmental biology
Acknowledgments
References
Optogenetic approaches to investigate spatiotemporal signaling during development
Optogenetic approaches
Introduction to light-responsive proteins
Applications of light-responsive proteins
Key advantages of optogenetic approaches
Tunability
Spatial control
Temporal control
Optogenetic applications in developmental signaling
How do signaling molecules spread through tissues?
Where is signaling required?
When is signaling required?
How do cells respond to different signaling amplitudes?
How do signaling dynamics generate diverse responses?
How does noise impact development?
How are simultaneous inputs from multiple pathways interpreted?
Practical considerations for optogenetic experiments
Conclusions and prospects
Acknowledgments
References
A matter of time: Formation and interpretation of the Bicoid morphogen gradient
Introduction
Dynamics of morphogen gradient formation
Morphogen production
Morphogen spatial distribution
Morphogen removal processes
Timescales of morphogen formation
Dynamics of Bcd morphogen formation
Bcd production
Bcd spatial distribution
Bcd degradation
Temporal dynamics of Bcd gradient formation
Summary of Bcd dynamics
Dynamics of morphogen gradient interpretation
Interpreting temporal changes in morphogen signal
Interpreting morphogen signal duration
Time window for interpretation
Bcd temporal interpretation and developmental precision
Bcd temporal integration
Time window for Bcd decoding
Bcd´s role as a genome organizer
Precise information transfer as a general paradigm in morphogen interpretation?
Conclusions
Acknowledgments
References
Constraints and limitations on the transcriptional response downstream of the Bicoid morphogen gradient
Introduction
The Bcd gradient
Positional information
The motility of Bcd molecules
The time it takes for Bcd to find its target sites on the hb promoter
Activation of transcription by Bcd
hb transcription dynamics
Visualizing hb transcription dynamics
Characterizing hb transcription dynamics
Transcription regulation of hb gene by Bcd proteins
Dissecting noise in hb transcription
Perspectives
Acknowledgments
References
Further reading
Formation, interpretation, and regulation of the Drosophila Dorsal/NF-κB gradient
Introduction
Components of the Dl morphogen network
Patterning events in oogenesis
The protease cascade
Toll signaling components
Dorsal/cactus interactions
Dl target gene expression
Domains of gene expression
Zelda
Twist
Regulation of the Dl gradient
WntD
BMP signaling
Size-dependent scaling of the Dl gradient
Quantitative measurements of the Dl gradient
Spatial extent of the Dl gradient
Dynamics of the Dl gradient
Mathematical modeling of the Dl gradient
Pioneering models of the Dl gradient
Deconvolution of nuclear Dl and nuclear Dl/Cact complex
Facilitated diffusion of Dl by Cact and Toll saturation
Modeling of Dl-dependent gene expression
Steady-state thermodynamic model of Dl target gene expression
Simulating spatiotemporal dynamics of gene expression using the Dl gradient as input
Modeling the effect of Zelda on gene expression
Conclusions and future perspectives
References
The design and logic of terminal patterning in Drosophila
Introduction
Signal transduction mechanisms in terminal signaling
Morphogenesis
Discussion
Acknowledgments
References
Dynamic positional information: Patterning mechanism versus precision in gradient-driven systems
Introduction
Positional information and developmental biology
Precision in patterning: Positional information as Shannon information
Patterning precision versus patterning mechanism
General relativistic positional information (GRPI)
Mechanisms for patterning precision
Conclusions
Acknowledgments
References
Intracellular morphogens: Specifying patterns at the subcellular scale
Introduction
The challenge of intracellular gradients-A consideration of length and time scales
State switching allows spatial activity gradients
Molecular gradients through differential diffusion
Toward self-organization
Controlling self-organization in space and time
Geometry sensing by patterning networks
Patterning and signal propagation across length scales
Gradient precision, noise, and readout strategies
Outlook
Acknowledgments
References
Insights into mammalian morphogen dynamics from embryonic stem cell systems
Introduction
The role of morphogens in mammalian gastrulation
ESC studies: Insights and opportunities
ESC systems for studying gastrulation
Do ligands function as morphogens in mammalian gastrulation?
How are changing morphogen concentrations interpreted in time?
How do morphogen systems result in spatial patterns of cell fates?
How are symmetries broken in the early embryo?
Conclusions
Acknowledgments
Appendix
Mathematical model for fate patterning by a single morphogen
Mathematical model for patterning multiple fates with two signals
References
Control of size, fate and time by the Hh morphogen in the eyes of flies
The small and large eyes in Drosophila rely on Hh
The range of Hh action is small and constant in different organs
A Hh-driven positive feedback loop induces a differentiation wave across the developing CE
Hh sets the stage for ocellus development
The ocellus, the small eye, is perhaps still too large for Hh
Stretching and linearizing a gradient
When a negative feedback ``log transforms´´ the gradient
A static morphogen source with a dynamic signaling works like a developmental metronome
Intrinsic constraints to the variation of ocellar size imposed by the gradient
Concluding remarks
Materials and methods
References
Genetic mechanisms controlling anterior expansion of the central nervous system
Introduction
Generation of CNS progenitors and proliferation modes: Drosophila
Progenitor (NB) generation
Progenitor (NB) proliferation modes
Generation of CNS progenitors and proliferation modes: Mouse
Progenitor generation
Progenitor proliferation modes
Anterior-posterior determinants of graded proliferation: Programmed cell death (PCD)
Drosophila
Mouse
Anterior-posterior determinants of graded proliferation: Hox genes
Hox gene expression patterns
Drosophila
Mouse
Hox genes suppress proliferation
Drosophila
Mouse
Anterior-posterior determinants of graded proliferation: Brain genes
Drosophila
Mouse
Anterior-posterior determinants of graded proliferation: PcG
Drosophila
Mouse
Temporal determinants of graded proliferation: Early and late factors
Drosophila
Mouse
An evolutionary ``fusion point´´ in the CNS?
Summary
Author contributions
Competing interests
Funding
References
Temporal dynamics in the formation and interpretation of Nodal and BMP morphogen gradients
Introduction
Gradient formation
Nodal
BMP
Gradient interpretation
Molecular sensing of ligand concentration and signaling duration
Outlook
Acknowledgments
References
Signaling regulation during gastrulation: Insights from mouse embryos and in vitro systems
The morphogenetic cell behaviors associated with gastrulation establish the blueprint of an organism
Signaling interactions during gastrulation
Technical hurdles to studying gastrulation
In vitro systems represent simplified gastrulation models
Micropattern differentiation
Embryoid bodies
PSC-extraembryonic stem cell aggregates
Critical signaling pathways at gastrulation
WNT signaling
BMP signaling
Activin/Nodal signaling
FGF signaling
Conclusions
References
Just passing through: The auxin gradient of the root meristem
Introduction
Proximo-distal maturation gradient of the root
Signals across cell walls
Plasmodesmata
Auxin
The auxin gradient of the root
Setting up the gradient
Positional inputs to the auxin gradient
Local auxin synthesis influences the root maximum
PLETHORAs mediate auxin but form their own gradient
Downstream auxin responses
Gene level regulation of PLTs
Protein level regulation of PLTs
PLTs show dose dependent effects
Direct outputs of the auxin gradient
Auxin has effects independent of PLTs
Prepatterned responses
Combinatorial inputs
Repressive lockdown states
Prospects
References
Further reading
Small RNAs as plant morphogens
Introduction
Small RNAs as mobile instructive signals
Opposing gradients of mobile small RNAs establish leaf polarity
A miR166 mobility gradient specifies cell fate within the root
miR394 mobility delineates the embryonic shoot stem cell niche
Reading out the gradient
Patterning properties of small RNA gradients are developmental-context dependent
Making the switch
Generating the small RNA gradient
Small RNA turnover
Regulation of small RNA mobility
Why so complicated?
Concluding remarks
Acknowledgments
References
Further reading