Analysis of the development of the nervous system of the zebrafish, Brachydanio rerio. II. The effect of nerve growth factor and its antiserum on the nervous system of the zebrafish.

Bueker (1948), investigating the effects of implanted tumors on the development of the nervous system of the chick embryo, found that sarcoma 180 caused enlargement (hypertrophy and hyperplasia) of the spinal ganglia in the segments adjacent to it. The motor columns, however, were not enlarged. He suggested that the sarcoma provided a selective periphery with mechanical and histochemical properties which favored sensory innervation. Subsequently other mouse sarcomas were found to have similar effects. Levi-Montalcini & Hamburger (1951) found that the sarcoma stimulated growth of the sympathetic ganglia to a greater extent than the spinal ganglia. Similar results were obtained when the tumor was grafted on to the chorioallantoic membrane, where the tumor and embryo share circulation but establish no direct contact, so it was hypothesized that a humoral factor from the tumor was responsible for the enlargement of the ganglia (Levi-Montalcini & Hamburger, 1953). Subsequently this group isolated a 'nerve growth stimulating factor' (NGF) from the sarcoma, and devised an in vitro bioassay in which NGF caused outgrowth of fibers from explanted embryonic spinal and sympathetic ganglia (Cohen, Levi-Montalcini, & Hamburger, 1954). The factor was subsequently detected and isolated from snake venom (Cohen & Levi-Montalcini, 1956) and from mouse submaxillary salivary glands (Cohen, 1960). An antiserum against this protein factor inhibits its action in tissue culture (Cohen, 1960). Daily subcutaneous injections of antiserum into a variety of mammals causes severe atrophy of the sympathetic chains (Levi-Montalcini & Booker, 1960) suggesting a normal role of NGF in the growth and maintenance of sympathetic neurons. Bueker, Schenkein & Bane (1960) have detected NGF in serum and in a variety of organs, especially in the axial region, of mouse and