Retinoic Acid: An Autocatalytic Morphogen

Abstract

Human development starts with the production of sperm and egg and ends with death. In between lie the embryo, the fetus, the child and the adult. Most developmental biologists are interested primarily in a short period of twelve weeks lying between fertilisation and fetus, The period of embryogenesis. During embryogenesis the fertilised egg cell develops into an immature form of the normal adult organism. A single relatively unspecialised cell will divide into 25 × 10⁹ cells, comprising a few hundred different cell types, arranged in a complex three dimensional pattern. During this period of human development three main cellular activities are involved. Firstly, the cells have to divide. Initially this is simple and repetitive, but gradually a complicated pattern of varying cell cycle times will emerge. Secondly, the cells must differentiate in different ways so as to produce the diversity of cell types. This involves both transcription of new genes and a progressive restriction of a cell’s potential differentiative paths. Thirdly, the different cell types must be arranged in an appropriate pattern so as to produce a functional embryo. Pattern formation can involve both decision making that leads to differential transcription and rearrangement of cells that have already differentiated. If we compare human development with common laboratory models it is clear that they consist of similar cells arranged in different patterns. A human embryo comprises much the same cell types as a monkey, a mouse, or even a magpie. The difference lies in the details of the three dimensional pattern as much as in the gene products. My main interest lies in factors that control this pattern.