REGULATED EXPRESSION OF THE NEUROFIBROMIN TYPE-I TRANSCRIPT IN THE DEVELOPING CHICKEN BRAIN

Neurofibromatosis type 1 (NF-1) is among the most common inherited diseases affecting cells of the central and peripheral nervous systems. A region of the NF-1 gene is similar in sequence to the ras-GTPase activator protein (ras-GAP), and investigations have confirmed that the NF-1 gene product (now known as neurofibromin) stimulates ras-GTPase activity in vitro and in vivo. Neurofibromin modulates the ability of ras proteins to regulate cellular proliferation and/or differentiation, suggesting a possible role in normal development. An alternative form of the neurofibromin transcript with an additional 63-bp exon inserted in the GAP-related domain (GRD) has been described recently. To determine whether differential expression of the two forms of neurofibromin GRD mRNA plays a role in embryonic development, we have isolated and characterized the corresponding chicken cDNA. The predicted amino acid sequence for the inserted exon is identical between chick and human, as are the exon-intron boundaries. RNase protection and RNA-polymerase chain reaction analyses demonstrate that most tissues express predominantly type II mRNA (which contains the insert) throughout embryonic development. In contrast, whereas type II is the major form in the brain early in development, expression of the type I transcript (without the insert) in this tissue increases dramatically at later times. Analysis of primary cultures derived from chick embryo brain indicates that the type I mRNA is enriched in neurons.