How embryonic tissues discriminate authentic morphogen gradients from self-generated pattern cues

Exogenous and endogenous patterning information are interpreted through the same canonical signalling networks during early development, yet most tissues reliably tell them apart. Developmental biologists have now mapped two discrete signalling hubs that prevent self-organised cues from being mistaken for external morphogen inputs, according to a study1 published in Development on 5 June. “Keeping the inner prepattern separate from bona-fide environmental instruction is essential for normal morphogenesis,” says co-author Lina Dervaux, a developmental biophysicist at Central Institute of Regenerative Science. “When that gatekeeping fails, we often see major birth defects or mis-patterned regeneration,” she adds. Dervaux and colleagues devised an assay to quantify the boundary at which embryonic epithelia confuse intrinsic and extrinsic information. Limb-bud explants were exposed to black-and-white stripes of retinoic-acid–soaked hydrogel with graded optical transparency over a stochastic background of inert matrix. In interleaved trials, the investigators used optogenetic CRISPR-dCas9 modules to induce endogenous activation of the same retinoic-acid–response genes, instructing the tissue to ‘imagine’ a stripe. Explants were then scored for whether they treated the stimulus as external (by orienting planar‐cell polarity and segmenting cartilage) and, if so, how robust the response appeared. When the internally evoked stripe produced higher local HoxA13 transcription, limb buds were more likely to polarise as though a real external gradient were present, regardless of whether retinoic acid had actually been supplied. The authors are attempting to measure—and ultimately model—an elusive concept: the dialogue between self-organised patterning and true environmental instruction, a topic that until now has been largely philosophical, notes Marc Nevalis, a tissue-engineering specialist at North Shore Research Institute.