Visualizing retinoic acid morphogen gradients
Morphogens were originally defined as secreted signaling molecules that diffuse from local sources to form concentration gradients, which specify multiple cell fates. More recently morphogen gradients have been shown to incorporate a range of mechanisms including short-range signal activation, transcriptional/translational feedback, and temporal windows of target gene induction.
Signals that determine multiple cell fates in a concentration-dependent manner are known as morphogens. Many of the major cell-signaling pathways studied in biology—Wnt, Fgf, Tgfb, etc.—work this way in some contexts.
how do sharp boundaries of gene expression form in the face of variability in signal production, cellular architecture, and environmental fluctuations?
The problem is more complex than it appears at face value. Recent studies have revealed unexpected dynamics of both ligand and response, positive and negative feedback, and mechanisms for scaling gradients to adjust for changes in tissue size and shape […]
Gene regulatory networks that specify different cell fates based on concentration may elicit different responses depending on regulatory mechanisms (eg, feedback) within the network
These regulatory mechanisms remain largely unknown for most putative morphogens.
the RA gradient to be surprisingly precise, robust, and able to induce sharp boundaries of target gene expression. However, these mechanisms cannot account for all of the robustness in the system
Future studies are needed to identify the other mechanisms that account for this remarkable adaptability.
Computational models also reveal a surprising beneficial role for noise in boundary sharpening–noise-induced switching.
Future studies will determine if similar noise-induced switching mechanisms control sharpening boundaries of target gene expression in response to other morphogens.
Common Design 