French flag model

Well-known morphogens include:

Some of the earliest and best-studied morphogens are transcription factors that diffuse within early Drosophila melanogaster (fruit fly) embryos. However, most morphogens are secreted proteins that signal between cells.

Morphogens are defined conceptually, not chemically, so simple chemicals such as retinoic acid may also act as morphogens.

Difficulties

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The basis of the French flag model is the idea that a morphogen autonomously forms a gradient with individual cells reading the concentration of the gradient. Cells then respond to a specific level of gradient with a specific differentiation to match the position the gradient indicates they are in. While widely accepted as an important model for understanding morphogenesis, it is not universally accepted by all developmental biologists. The difficulties with all gradient based models of morphogenesis were extensively reviewed by Natalie and Richard Gordon and include seven^[5] specific points:

1. In order to maintain a gradient at steady state there has to be a sink i.e. a way in which diffusing molecules are destroyed or removed along the way and/or at some boundaries. Sinks are rarely, if ever, even considered when the gradient model is invoked.
2. Diffusion must occur in a confined space if a gradient is to be established. However, many organisms such as the axolotl develop normally even if the vitelline membrane and jelly layers are removed and development occurs in flowing water.
3. Diffusion is temperature dependent yet development can proceed normally over a wide variety of temperatures in animals whose eggs develop external to the mother.
4. Diffusion gradients do not scale well yet embryos come in variety of sizes.
5. Diffusion gradients follow the superposition principle. This means that a gradient of one substance in one direction, and a gradient of the same substance in a perpendicular direction, result in a single one-dimensional gradient in the diagonal direction, not a two dimensional gradient. Developmental biologists frequently invoke a two dimensional gradient even though a two dimensional gradient system requires two morphogen gradients with two different sources and sinks placed approximately perpendicular to one another.
6. Fluctuations in gradients always occur, especially at the low concentrations commonly found during embryogenesis, making a specific response by an individual cell to particular concentration thresholds problematic.
7. Each cell has to be able to “read” the morphogen concentration accurately, otherwise boundaries between tissues become ragged. Yet such ragged boundaries are rare in development.

References