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Signaling molecules affecting patterning processes are usually proteins and rarely peptides. Two novel peptides, pedibin and Hym-346, that are closely related to one another have been isolated from Hydra vulgaris and Hydra magnipapillata. Several experiments indicate that both cause a reduction in the positional value gradient, the principle patterning process governing the maintenance of form in the adult hydra. The peptides cause an increase in the rate of foot regeneration following bisection of the body column. Treatment of animals with either peptide for an extended period of time resulted in an apical extension of the range of expression of CnNk-2 along the body column. Such an extension is correlated with a decrease in positional value. Transplantation of tissue treated with Hym-346 results in an increase in the fraction forming feet, and aggregates derived from Hym-346 tissue form more feet and fewer heads. The latter two experiments provide a direct measure of the lowering of positional value in the treated tissue. These results suggest that peptides play signaling roles in patterning processes in cnidaria and, plausibly, in more complex metazoans as well.

Foot-specific differentiation processes in hydra are controlled by activating and inhibiting potentials. In an attempt to understand the molecular mechanisms underlying these processes, two substances were isolated from Hydra vulgaris that stimulate foot-specific differentiation measured as acceleration of foot regeneration. These sub-stances were shown to be peptides of 13 and 21 amino acids, respectively, with sequences that bear no significant homology to known peptides or proteins. Polyclonal antibodies were raised against both peptides. The data obtained by biological and radioimmunoassays show that the shorter peptide, pedin, is an excellent candidate for a major component of the ‘foot-activating potential’.

In hydra, HA is produced by nerve cells and released into the intercellular space bound to large-molecularweight carrier(s). By additional interaction with extracellular matrix components and selfinactivation by dimerisation, a local action is ensured. HA acts as a mitogen on all dividing cell types in hydra forcing them to pass through G2, divide, and either start a new round of cell division or terminally differentiate. In addition, HA is required for head-specific determination and differentiation processes. To become a head-specific nerve cell, for example, an interstitial stem cell requires HA in early S-phase to become determined to the nerve cell pathway, in late G2 to progress through mitosis, and/or in G1 to differentiate to a head-, and not to a foot-, specific nerve cell. HA (with identical amino acid sequence) occurs in other animals including mammals. In mammals, it is produced by nerve or endocrine cells and it probably acts, as in hydra, on nerve-precursor cells. On the neural cell line NH15-CA2 and on the pituitary cell line AtT20, HA acts as mitogen by stimulating cells arrested in G2 to enter mitosis. The presence of HA early in neural development and in abnormal neural development, such as in brain and neuroendocrine tumors, are consistent with a function in growth control for HA in mammals.