Extra-genomic instructive influences in morphogenesis: A review of external signals that regulate growth and form

Embryonic development and regeneration accomplish a remarkable feat: individual cells work together to create or repair complex anatomical structures. What is the source of the instructive signals that specify these invariant and robust organ-level outcomes? The most frequently studied source of morphogenetic control is the host genome and its transcriptional circuits. However, it is now apparent that significant information affecting patterning also arrives from outside of the body. Both biotic and physical factors, including temperature and various molecular signals emanating from pathogens, commensals, and conspecific organisms, affect developmental outcomes. Here, we review examples in which anatomical patterning decisions are strongly impacted by lateral signals that originate from outside of the zygotic genome. The endogenous pathways targeted by these influences often show transgenerational effects, enabling them to shape the evolution of anatomies even faster than traditional Baldwin-type assimilation. We also discuss recent advances in the biophysics of morphogenetic controls and speculate on additional sources of important patterning information which could be exploited to better understand the evolution of bodies and to design novel approaches for regenerative medicine.