HUlip is a human homologue of a C. elegans gene, unc-33, that is developmentally regulated during maturation of the nervous system. HUlip is highly expressed only in the fetal brain and spinal cord, and is undetected in the adult brain. The purpose of this study was to investigate the pattern of hUlip expression in the developing human brain and
nervous system tumors. Ten human brains at different developmental stages and 118 cases of
nervous system tumor tissues were examined by immunohistochemistry. Twelve related tumor cell lines were also analyzed by northern blotting and immunoblotting. HUlip was expressed in late fetal and early postnatal brains; strongly in the neurons of the brain stem, basal ganglia/thalamus, and dentate gyrus of the hippocampus, and relatively weakly in the cerebral and cerebellar cortex. Among
tumors, hUlip expression was easily detected in
tumor cells undergoing neuronal differentiation such as
ganglioneuroblastomas and
ganglioneuromas. Furthermore, hUlip immunoreactivity was also found in various
brain tumors showing neuronal differentiation:
central neurocytomas (6 of 6 cases were positive),
medulloblastomas (5/11), atypical
teratoid rhabdoid tumor (1/1) and
gangliogliomas (4/7). Some astrocytic
tumors also showed weak positivity:
astrocytomas (1 of 5 cases),
anaplastic astrocytomas (2/5), and
glioblastomas (3/11). Subependymal giant cell
astrocytomas and
subependymomas, which are of controversial histogenetic origin, showed strong hUlip immunoreactivity. The results of this study indicate that the expression of hUlip
protein is distinctly restricted to the late fetal and early postnatal periods of human nervous system development and to certain subsets of
nervous system tumors. The exact function of hUlip needs to be further clarified; yet the results of our study strongly imply that hUlip function is important in human nervous system development and its aberrant expression in various types of
nervous system tumors suggests a role of hUlip as an oncofetal neural
antigen.