THE KROX-20 TRANSCRIPTION FACTOR IN THE RAT CENTRAL AND PERIPHERAL NERVOUS SYSTEMS - NOVEL EXPRESSION PATTERN OF AN IMMEDIATE-EARLY GENE-ENCODED PROTEIN

The KROX-20 protein (also termed EGR-2) is encoded by an immediate ear ly gene cloned by cross-hybridization to the Drosophila melanogaster K ruppel gene. It belongs to a class of transcription factors with zinc finger motifs and binding activity to a transcriptional regulatory DNA element termed the early growth response consensus sequence. In the p resent study the temporospatial expression of KROX-20 was investigated in the central and peripheral nervous systems of normal rats and afte r various stimuli known to induce immediate early genes, including epi leptic seizures, axotomy, pharmacological treatment with glutamate and alpha-adrenergic receptor antagonists, and peripheral noxious stimula tion. Immunocytochemistry was performed with a specific polyclonal ant iserum generated against a fusion protein containing KROX-20 sequences . In the central nervous system, KROX-20 protein demonstrated distinct constitutive nuclear expression in specific neuronal subpopulations o f the cortex, septum, amygdala, olfactory bulb and hypothalamus. In ad dition, distinct cytoplasmic immunoreactivity was present in spinal an d medullary motoneurons, dorsal root ganglion neurons and a few neuron al cell populations of midbrain and forebrain. In the CNS, KROX-20 was only induced by bicuculline-induced epileptic seizures. Topographical ly, the postictal increase of KROX-20 levels was restricted to areas w ith constitutive expression, such as cerebral cortex, fornix and amygd ala. Induction of KROX-20 peaked at 4-8 h after onset of seizure activ ity. No increase in immunoreactivity was observed in the hippocampus, the brain region most severely affected by bicuculline-induced seizure s. Transection of central and peripheral nerve fibers did not result i n KROX-20 induction in axotomized neurons. However, KROX-20 was induce d in Schwann-like cells after transection of the sciatic nerve. In con trast to KROX-20, KROX-24, a related transcription factor of the zinc finger family, was markedly induced in hippocampal and spinal neurons following seizures and peripheral noxious stimulation, respectively, a s well as in CNS neurons following axotomy. Our data indicate that KRO X-20 represents an immediately early gene product with basal expressio n in selected neuronal populations of the nervous system and a restric ted inducibility after intentional stimuli.