"A gradient model for proximo-distal differentiation in vertebrate limbs"
The development of a multicellular organism rises extremely interesting and challenging questions such as how are the highly reliable and robust processes of morphogenesis achieved and which mechanisms control pattern formation. The developing vertebrate limb bud is an excellent model to study both theoretically and experimentally pattern formation during embryogenesis. The limbs develop from small protrusions that arise from the body wall of the embryo and differentiation proceeds distally as the limb extends. There are several theoretical models for pattern formation in the developing vertebrate limb based on reaction-diffusion mechanisms, morphogens or mechano-chemical interactions. We present a model for proximo-distal differentiation in the limb bud based on a robust spatiotemporal gradient that allows the cells to progressively differentiate and which explains the phenotypes of several mutations and manipulations. The robustness of the gradient is analysed. Moreover, the existence of other genetic information specifying the proximo-distal fate is underscored both theoretically and experimentally. Finally, our model is compared with already existing models for the proximo-distal differentiation, the Progress Zone model and the early-specification model.