Lecture 11 Morphogens and Gradients

Morphogens, Gradients, and Developmental Specification

• Overview of Morphogens and Gradients

• Importance of Gradients in Development

  • Regulate genes and transcription factors

  • Influence cell differentiation

Morphogen Definition

• A morphogen is a diffusible molecule affecting cell movement and organization during development.

• Key roles:

  • Establishing polarity in embryos

  • Specifying cell identity in tissues

Morphogen Gradients

• Gradients can vary drastically (25-50 fold) but often only a small (2-3 fold) change is required for gene expression alteration.

• Morphogens effective at low concentrations (10^-9 to 10^-11 M).

Key Components of Morphogen Implementation

• Source of morphogen

• Morphogen threshold concentrations

• Position within the embryo

French Flag Model of Morphogen Gradients

• A single morphogen can create multiple cell types.

• Required elements:

  1. Morphogen gradient

  2. Multiple thresholds for response

Real World Gradients

• Illustrated with examples from biological systems.

• Factors include different sources, thresholds, and distances affecting morphogen concentration.

What Makes a Molecule a Morphogen?

• For a diffusible molecule to be considered a morphogen, it must be demonstrated that :

• 1. Cells respond directly to that molecule.

• 2. The differentiation of those cells depends on the concentration of that molecule.

• This could be a hormone, but there are other examples such as proteins (example is the Zebrafish Nodel protein)

Morphogen Levels and Thresholds

• Different distributions from one morphogen can lead to diverse outcomes.

• Morphogen levels can have varying impacts based on surrounding gradients.

The Protein Nodal Functions as a Simple Morphogen

• Nodal (Morphogen) regulates the expression of other genes over a gradient like the French Flag.

• Nodal Level Other Gene Regulation

  • High = Goosecoid

  • Medium = Float Head

  • Low = No-Tail

Simple Threshold Model:

• Bicoid (Morphogen) Regulates Hunchback (Gene Expression)

  • Hunchback (hb), responds to the dose of bicoid protein

  • Concentration above threshold level activates the expression of hb

• The more bicoid transcripts, the further back hb expression occurs in the embryo

  Establishing a “Stripe” of Expression in an Embryo

• Kruppel gene expression needs threshold levels to be in the “just right” range

• (concentrations of hunchback must be above a level to be activated, but below another level to not be repressed

Mechanisms Driving Differential Gene Regulation

• Differential Binding Site Affinity

  • Variability in binding affinity alters gene activation or repression.

• Combinatorial Input

  • Together with enhancers and repressors, morphogen involvement activates genes.

• Feed Forward Loop

  • Morphogen activates a gene which then influences another target gene.

• Positive Feedback

  • Original gene activation can persist even without morphogen presence.

• Cross Repression

  • Two morphogens can inhibit each other's expression to create specific patterns.

• Reciprocal Repressor Gradient

  • Two gradients working against each other dictate gene outcomes.

Temporal Dynamics of Gradients

• Gradients are dynamic; their concentrations can change over time, affecting gene expression significantly.

• Importance of recognizing that morphogen gradients are not static.