In the 1960s Lewis Wolpert devised a model to describe basic pattern formation in development. This model was known as the French Flag Model. It is a useful model as the formation of the three colours of the flag can be used to understand the formation of the three germ layers present in embryos. The first thing to note is that no matter what size the flag, it still maintains the same basic pattern. One third will be blue, one third white and one third red, in that order, along one axis. Second, in a line of cells with defined boundaries, each cell has the potential to differentiate into a blue, white or red cell. Wolpert set out to try and explain the mechanism behind how the cells know which colour they should differentiate into. Cells must receive some form of information to deduce where they are situated within the flag model, and then according to their genetic program interpret this information by differentiating into one of the three cell types.

There are two stages of pattern formation, first the cells have to establish their position and then they have to interpret this information. The fact that a clear distinction has been made between these two processes implies that there is no set relation between a cells position and the how it interprets the information it is sent. Thus in a different set of parameters these cells are capable of producing a completely different pattern. Wolpert devised a simple way to explain how a cell establishes its orientation, based on the gradient of a substance. If the concentration of a chemical substance decreases from one end of the flag to the other a cell could work out where exactly it was positioned in relation to the boundaries. This would be due to the amount of chemical substance the cell received. This Chemical substance is known as a Morphogen. Morphogens are described as substances in embryonic tissues that form a concentration gradient and influences morphogenesis.

In the French Flag Model we assume the concentration is greatest at one end and lowest at the opposite end and so the morphogen diffuses at a constant rate down the line of cells. It is also safe to assume that the cells respond to threshold concentrations of the morphogen. Above a particular concentration threshold blue cells will form, whilst below this concentration threshold but above another, white cells will form. Below both these concentration thresholds red cells form creating the complete French Flag pattern.

The threshold could be one of two things; the specific amount of morphogen need to bind to receptors on the cells in order to activate intracellular signalling cascades, or differing concentrations of transcription factors, which are required to activate certain genes within the cells.

This model highlights two important features of morphogenesis. Firstly, even if the length of the line of cells varies, patterns will still from in the correct proportions, as long as defined boundaries are present with constant but differing concentrations of morphogen at either end. Secondly the pattern could regenerate itself to the complete original form after being cut in half, as long as the defined boundaries and concentrations were re-established. 

[Adapted from Wolpert Principles of developmental Biology]

Retinoic acid gradient visualized for the first time in an embryo

Researchers from the RIKEN Brain Science Institute in Japan report a new technique that allows them to visualize the distribution of retinoic acid in a live zebrafish embryo, in real-time. This technique enabled them to observe two concentration gradients going in opposing directions along the head-to-tail axis of the embryo, thus providing long-awaited evidence that retinoic acid is a morphogen.

A morphogen is a substance governing the pattern of tissue development in the process of morphogenesis, and the positions of the various specialized cell types within a tissue.

Since morphogens diffuse through the tissues of an embryo during early development, concentration gradients are set up. These gradients drive the process of differentiation of unspecialised (stem) cells into different cell types, ultimately forming all the tissues and organs of the body.

The famously prolific mathematician Alan Turing had hypothesized that such biological patterns arise when a pair of chemicals react in a regular, alternating manner as they move through tissue during development. In February Jeremy Green and his team at King’s College London identified a pair of proteins called morphogens that shape the ridges on a mouse’s palate. These morphogens, named fibroblast growth factor and sonic hedgehog, form an “activator” and “inhibitor” pair that together differentiate cells into ridges and troughs. The researchers believe that the same alternating chemical process stimulates skin cells to generate patches of differently colored fur.
Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms

Gradients of the secreted morphogen Sonic Hedgehog (Shh) pattern the neural tube in vertebrates. Cohen et al. quantify Shh signalling in developing mice, and by constructing a computational model of the process, identify mechanisms by which the dynamics of Shh signalling are regulated.
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“I’m changing, I’m spinning. Morphogenic.
I’m webbing I’m morphing. Morphogenic.
I’m hungry, I’m thirsty. Morphogenic.
I’m tired, I’m wasting. Morphogenic.”