NEURONAL CELL NUCLEAR FACTOR - A NUCLEAR RECEPTOR POSSIBLY INVOLVED IN THE CONTROL OF NEUROGENESIS AND NEURONAL DIFFERENTIATION

We have cloned from a cDNA library of neuronal derivatives of retinoic -acid-induced embryonic carcinoma cells a nuclear receptor that may be involved in the control of late neurogenesis and early neuronal diffe rentiation. The receptor which is practically identical in sequence wi th germ cell nuclear factor, has been designated neuronal cell nuclear factor (NCNF). NCNF is exclusively expressed in the neuronal derivati ves of PCC7-Mz1 cells, with the expression beginning within hours of e xposure to retinoic acid. In the developing mouse brain, NCNF is expre ssed in the marginal zones of the neuroepithelium which are known to c ontain young postmitotic neurons. NCNF binds to the DRO sequence there by silencing transcription. Because NCNF does not recognize hormone re sponse elements of other nuclear receptors tested and does not heterod imerize with these, it probably binds exclusively as a homodimer. NCNF may induce neuronal differentiation by repressing the activity of gen es that permit cell fates other than the neuronal one.