Morphogen gradients can convey position and time in growing tissues

Abstract

During development, cells need to make fate decisions according to their position and the developmental timepoint. Morphogen gradients provide positional information, but how timing is controlled has remained elusive. Here, we show that in morphogen gradients with constant decay length, cells experience transient, hump-shaped concentration profiles if the morphogen source expands in parallel with the uniformly growing tissue. This transient signal can convey time. We further show that opposing steady-state morphogen gradients with equal decay length, as found in the vertebrate neural tube, can synchronise cell fate decisions along the entire expanding patterning axis, because the product of the two opposing concentration gradients is constant along it. In case of an increasing amplitude, cells experience a transient hump signal, while in case of constant gradient amplitudes, the concentration product declines continuously as the tissue expands — a hallmark of a depletion timer. Once the tissue reaches a critical size and the concentrations a critical value, a cell fate switch can be triggered. Timers based on morphogen gradients offer a simple mechanism for the simultaneous control of position and time and might apply in many patterning systems, as uniform growth is observed widely in development.