Role of the neuropeptide head activator for growth and development in hydra and mammals.

In hydra, HA is produced by nerve cells and released into the intercellular space bound to large-molecular-weight 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.