Morphogen Gradient & Tissue Patterning Flashcards
What are spatial instabilities, and how do they occur?
Spatial instabilities occur when a system exhibits heterogeneous behaviour across space, leading to the formation of distinct patterns or structures in a spatial domain.
What are temporal instabilities, and how do they occur?
Temporal instabilities refer to fluctuations or oscillations over time rather than space. These can manifest as periodic or chaotic behavior in a system’s dynamics.
How do spatial vs temporal instabilities come about?
Spatial instabilities = local positive feedback and long range inhibition
Temporal instabilities = local positive feedback and negative feedback with a delay
Explain the difference between self-organized vs programmed development
Self-organized development means complexity emerges from local interactions
Programmed development means existence of a plan, complexity is embedded beforehand
Give and example of self-organized development
Zebrafish embryo
Self-organized segmentation = multi-scale integration to form the clock((synchronization) and wavefront
Give an example of programmed development
Drosophila embryo
Programmed segmentation = hierarchical biochemical sequence
What model does Wnt-DKK/BMP depict?
Reaction-diffusion model based on simple chemical diffusion
Wnt is the short ranged autoactivator and activates DKK/BMP
DKK/BMP is the long-range inhibitor
What happens when DKK is overexpressed?
WNT and its inhibitor DKK as primary determinants of murine hair follicle spacing, using a combined experimental and computational modeling approach.
Transgenic DKK overexpression reduces overall appendage density.
Moderate suppression of endogenous WNT signaling forces follicles to form clusters during an otherwise normal morphogenetic program
What model is Notch-Delta based on?
Reaction-diffusion model based on CELL-CELL CONTACT
What describes RD models based on cell movement?
RD wave on the skin of marine angelfish
Two different coloured cells (melanophores) when partially ablated will react and regenerate based on self-orgnaization
If the RD model is not limited to molecules, what else can it be applied to?
Cell motion
Mechanical forces
In Turing patterns how is symmetry broken?
Through feedback and self-roganization
What happens if there is asymmetry in the system to begin with?***
Define positional information
In developmental biology, refers to the concept that cells in a developing organism can interpret their location within a spatial coordinate system and adjust their behaviour accordingly.
This process is crucial for the proper organization and differentiation of cells during embryonic development.
What is Francis Cricks model for positional information?
Source and sink model
What is the French Flag model and how does it differ from source-sink model?
There is no sink but a degradation in the system as the molecules travel away = exponentially decaying function as chemical get further away from the cell
What is the decay length and its equation?
Lambda = decay length = sqrt (D/k)
Define signal interpretation
How cells will change their fate depending on morphogen gradient
Magnitude and duration of the morphogen signal can activate different gen regulatory networks
Why don’t cells just revert when the signal is no longer present?
Memory is retained to ensure the cell doesn’t forget its identity
This is carried out due to positive autoregulation = bistability
What is important about double positive/negative feedback loops?***
Either both are ON or OFF
Important for decision-making
What is the lock-on mechanism?
Lock-on mechanism in double positive and negative feedback loops facilitates robust decision-making in developmental processes.
Positive feedback amplifies specific cell fates, while negative feedback provides stability and control, leading to irreversible commitments that are essential for the proper organization and function of developing tissues.
This mechanism ensures that once a cell has made a decision about its fate, it is effectively locked into that state, supporting the intricate patterns and structures observed in biological systems.
What properties do 3-node motifs have?
Regulated feedback
Memory, persistence and bistability
Why do transcriptional cascades generally have 3 different kinases/signalling molecules?
Temporal Delay = blocks transient signals
Amplification = small initial signal leads to large output
Why are transcriptional cascades important in developmental networks?
Timescale of transcription cascades is well suited to guide developmental processes
Give two examples of positional information models in development
Drosophila segment development = bicoid forms a morphogen gradient
Drosophila fly wing disc
What is bicoid?
Morphogen and transcription factor
What is the function of bicoid
Establishes anterior-posterior axis of drosophila embryo by diffusing away from the anterior
Bicoid mRNA situated at anterior of fruit fly egg during oogenesis
A series of genes get switched on in a temporal manner, causing spatial patterns to form
What can proliferation rate determine?
Shape or size of tissue is determined by how fast the cell divides
Name the two factors morphogen gradietns can control
Cell proliferation rate (cell growth)
Cell differentiation
What pathway is Dpp found in, and what is its function??
Dpp controls growth
Via Hipp/Yorkie signalling pathway
What happens to the morphogen gradients as the cell grows?
The morphogen gradient scales as cell grow to keep the correct proportions
What is an EXPANDER and how does it interact with morphogen gradient expansion?
Expander degrades morphogen
As cell grows (undergoes cell division), expander concentration drop (diluted)
Degradation of morphogen decreases, so morphogen gradient expansion increases
What feedback is gradient scaling explained by?
Positive feedback
Expander inhibits morphogen gradient expansion
Morphogen gradient expansion inhibits decay by dilution of expander due to cell growth/division
What is the difference between RD upstream vs downstream of PI? ***
The reaction diffusion lays the groundwork for positional information
Positional information tells reaction-diffusion where to act
What is the role of symmetry breaking?
To create asymmetric organs
What are the molecules that generate left-right patterning of the heart, and what is their feedback loop?
Nodal-Lefty 2
Nodal = autoactivator and activates Lefty2
Lefty2 = inhibitor of Nodal
What model is left-right patterning?
It is a large diffusion-reaction model, NOT positional information
High concentration of Nodal on left and low concentration on right, since Lefty2 restricts spread of Nodal to the right side
How do cilia play a role in symmetry breaking?
Cilia are found on teh left-right organizer
Motile cilia move rapidly to create leftward direction flow of extracellular fluid
Flow is sensed by immotile (primary) cilia which are mechanoreceptors
Define mechanoreceptor
Structure or protein that detect mechanical forces and transforms them into biochemical signals
Example of RD upstream of PI
Nodal-Lefty2, which constitutes a Turing system
Example of RD in parallel with PI
Limb bud formation due to Shh as key morphogen to establish body plan
How does Shh signalling and BMP-Wnt-Sox9 generate differnt digits?
Shh is positional information
BMP-Wnt-Sox9 is reaction diffusion
Example of RD downstream of PI
Limb formation by Hox genes and FGF
Downstream in this context means that these systems rely on previously established positional cues to guide further development.
