Effects of eye removal at birth on histogenesis of the mouse superior colliculus: An autoradiographic analysis with tritiated thymidine

When a peripheral organ or a part of the nervous system is lost during development, related parts of the nervous system may be abnormally small. Attention has been given particularly to the effects of eye removal on development of visual centers of the brain, since the studies of Gudden (1870, lSSl ) , and von Monakow (1889). Small size of visual centers has been found after eye removal in fish and amphibia (Piatt, ’48; McMurray, ’54; Weiss, ’55; Filogamo, ’60), birds (Hamburger and Levi-Montalcini, ’50; Filogamo, ’50), and mammals (Clark, ’42; Hess, ’57; Matthews, Cowen, and Powell, ’60), including man (Goldby, ’57). The small size of the brain part has often been ascribed to “hypoplasia,” though it might result from any of several causes, singly, or combined. A classification of these causes includes decreased proliferation of cells (numerical hypoplasia), arrest of maturation of cells (usually resulting in volumetric hypqplasia), loss of cells already formed (degeneration), secondary decrease in size of cell bodies (atrophy of cell bodies), and secondary decrease in volume of neuropil (atrophy of cell processes). No consistent terminology for these cell responses has been adopted, and only in recent years have careful attempts been made to specify which cellular events might be responsible for the “hypoplasia. ” Levi-Montalcini (’49) analyzed the cellular events in the acoustic and vestibular centers after removal of the otocyst in chick embryos. She concluded that “the hypoplasia is largely, if not entirely, due to regression of partially differentiated neurons,” while “the initial phases of determination and proliferation . are independent of ingrowth of root fibers . ,” Filogamo (’50) recognized a comparable situation when he removed an eye from chick embryos after about 50 hours of incubation. The optic tectum developed normally until about the fourteenth day and then regressed. On the other hand, Kollros (’53) found decreased cell proliferation to account for the small size of the contralateral optic lobe after he removed an eye from frog larvae. He also noted briefly that removal of an eye at late larval stages resulted both in a decreased number of subsequent cell divisions and in a failure of maintenance of cells already formed. The varied results of these and other investigations are commonly thought to reflect species differences or differences in the stage of brain development at which the peripheral sense organ is lost. Autoradiographic methods allow study of the behavior of cells in the developing brain with greater precision than was previously possible. Tritiated thymidine (thymidine-I-13) injected into mammals is available to cells for less than one hour and is incorporated selectively into cells synthesizing deoxyribonucleic acid (DNA) preparatory to cell division; the tritium is then distributed to the DNA of the daughter cells equally and remains constant in amount per cell nucleus unless diluted in half during each subsequent cell division (Hughes et al., ’58) . In the developing mammalian brain, the autoradiographic method allows analysis of the number of cells forming, their locations, the patterns and timing of their subse-