Morphogen

A morphogen is a signal whose spatial concentration helps specify different biological cell fates or behaviors during biological development. A morphogen gradient provides a positional cue: biological cells at different distances from a source experience different local concentrations and can follow different developmental pathways. A spatial concentration variation alone does not establish that a substance is a morphogen; its graded developmental effects matter. See Alberts et al., Molecular Biology of the Cell, 4th edition (2002): morphogens as graded developmental signals.

The beautiful idea is that one distributed signal can help organize several regions of a developing body. A continuous morphogen gradient can supply the input for distinct domains of gene expression, rather than requiring a separate signal for every position. A morphogen response threshold is a useful idealization of that interpretation: high, intermediate and low concentrations are assigned different outcomes. The morphogen reaction-diffusion equation describes one way to generate a morphogen gradient; the equation is a model of transport and reaction, while the morphogen is the signal being transported.

Detection and interpretation also depend on the receiving biological cell. For an extracellular morphogen, receptors and signal transduction connect the local concentration to a response; receptor binding occupancy is only one step in that connection. The same morphogen gradient can be interpreted differently in different tissues because their developmental context differs. Thus a morphogen response threshold summarizes a particular response in a particular context, rather than being a universal property of the signal. See Scott F. Gilbert, Developmental Biology, 6th edition (2000): positional information and context-dependent interpretation.

An important experimental example came in 1988. Wolfgang Driever and Christiane Nüsslein-Volhard used antibodies to examine the bicoid protein in early fruit-fly embryos. They reported a concentration profile approximately described by an exponential function, highest at the front, with the protein concentrated in cell nuclei. Their abstract proposed diffusion from localized messenger RNA and dispersed degradation as a likely origin of the morphogen gradient, rather than proving a unique transport mechanism. ^[ref]

In a companion study, Driever and Nüsslein-Volhard genetically changed the amount and distribution of bicoid messenger RNA, measured the resulting protein morphogen gradient, and compared developmental maps. Increased local bicoid protein levels shifted prospective anterior structures toward the rear; decreased levels shifted them toward the front. This linked a measured concentration profile to positional effects in biological development. The toy calculations below illustrate that logic with arbitrary numbers, not measured bicoid parameters. ^[ref]