In preprints: morphogens in motion

Morphogen gradients represent one of the most influential ideas in developmental biology. Although the original notion of a morphogen can be traced back more than 80 years, to at least Dalcq and Pasteels' suggestion that gradients of ‘morphogenetic substances’ guide the differentiation path of cells during embryogenesis (Dalcq and Pasteels, 1937), the concept has evolved over the years (Stapornwongkul and Vincent, 2021). In its current formulation, a morphogen is considered to be a chemical signal that spreads from a localised source to form a concentration gradient in a tissue. Cells within the gradient read the local morphogen concentration to acquire a specific fate. In this view, a morphogen gradient needs to span multiple cell diameters to impart positional information in the developing tissue. Consequently, much attention has focused on how morphogens spread.A dominant model in the field, the so-called hindered diffusion model, postulates that morphogens diffuse freely in the extracellular space, but that tissue geometry and transient binding interactions affect spreading (Stapornwongkul and Vincent, 2021). Therefore, one can distinguish between free (or local) and effective diffusion rates. Whereas free diffusivity depends on the molecule's size, temperature and viscosity of the environment, effective diffusivity takes into account the effect of morphogen binding and unbinding to receptors on cell surfaces and in the extracellular matrix. Free diffusivity has been successfully measured in a range of model systems using fluorescence correlation spectroscopy (FCS), a method that assays the average time a fluorescently labelled molecule takes to pass through a very small volume (更多