DIFFERENTIAL INDUCTION OF PAX GENES BY NGF AND BDNF IN CEREBELLAR PRIMARY CULTURES

The Pax genes encode sequence-specific DNA binding transcription facto rs that are expressed in embryonic development of the nervous system. Primary neuronal cell cultures derived from the cerebellar cortex of e mbryonic day 14, newborn and 7-d old mice, were used to investigate th e cell-type specific expression patterns of three members of the murin e paired box containing gene family (Pax gene family), in vitro. Cell types which express Pax-2, Pax-3, and Pax-6 RNA in primary cultures co rrespond to those found in regions of the cerebellum which show RNA si gnals in sections of the developing mouse brain. To find mechanisms re gulating Pax gene expression during cerebellar development, the differ ential regulation of Pax-2, Pax-3, and Pax-6 by NGF and BDNF, two stru cturally related neurotrophins, was studied in such primary cultures. Pax-2 and Pax-6 RNA increased slightly by 1 h and remained elevated th roughout a 24-h treatment with BDNF and NGF. Pax-3 RNA was not detecte d in newborn cultures, but underwent a rapid (I h) and transient (2 h) induction upon treatment with either BDNF or NGF. No response was see n with EGF or FGF. Cycloheximide treatment amplified Pax-3 induction a nd prolonged the signal. Thus, Pax-3 induction resembles that of the i mmediate-early gene c-fos, which transduces growth factor signals duri ng the development of particular neuronal/glial cell types. The change s in Pax expression were inductive rather than trophic.