EXPRESSION OF THE NEUROFIBROMATOSIS-1 (NF1) ISOFORMS IN DEVELOPING AND ADULT-RAT TISSUES

The neurofibromatosis 1 (NF1) gene encodes a large M(r) similar to 250 ,000 phosphoprotein, the expression of which in adult tissues is limit ed to neurons, Schwann cells, oligodendrocytes, adrenal medulla, and l eukocytes. The presence of two alternatively spliced exons (23a and 48 a) in the NF1 gene allow for the generation of four possible neurofibr omin isoforms. Type 1 neurofibromin contains neither 23a or 48a exon s equences, while type 2 neurofibromin contains only the 23a exon insert ion. Previous studies have demonstrated that types 1 and 2 neurofibrom in might have different functional properties relative to microtubule association and GTPase-activating protein activity towards p21-ras. To determine the normal pattern of expression of these NF1 isoforms, the adult and developmental expression of types 1 and 2 NF1 was examined. Herein, we demonstrate that NF1 mRNA is expressed at varying levels i n adult tissues and is developmentally regulated during embryogenesis. Neurons in the central nervous system express predominantly type I NF 1. Using mouse neocortical cultures enriched for neurons or glial cell s, type 1 NF1 predominance was demonstrated in neurons, while type 2 N F1 predominated in glial cells. In contrast to central nervous system neurons, neurons expressing the type 2 NF1 isoform were identified in the developing dorsal root ganglia and spinal cord by in situ hybridiz ation using a type 2-specific oligonucleotide probe. The elucidation o f the differential expression pattern of these two NF1 isoforms during development and in adult life provides the foundations for future stu dies aimed at determining the functions of these neurofibromin isoform s.