Neurofibromin, a predominantly neuronal GTPase activating protein in the adult, is ubiquitously expressed during development

Abstract

The onset of manifestations of the common, autosomal dominantly inherited disease type 1 neurofibromatosis (NFl) is usually in childhood. To begin to understand the pathogenesis of NF1, we analyzed the developmental pattern of expression of the protein product of the NF1 gene, neurofibromin, by Western blotting and immunohistochemistry using the rat as a model system. Neurofibromin is uniformly distributed throughout embyronic day 10 and 12 rat embryos. By embryonic day 16, neurofibromin immunoreactivity is enriched in neurons of the cortical plate, in peripheral ganglia, and in developing CNS and PNS fiber tracts, but remains detectable outside the nervous system. Expression decreases in nonneural tissues by postnatal day 6, and neurofibromin is greatly decreased (lung, adrenal cortex, skin) or absent (skeletal muscle, cartilage) in adult tissues except for brain, spinal cord, peripheral nerve, and adrenal medulla. Transient expression of neurofibromin during development in many tissues suggests the importance of this GTPase-activating protein in morphogenesis and organ growth. A separate role is proposed for neurofibromin in growing axons and in the mature nervous system. 0 1993 Wiley-Liss, Inc.

Neurofibromatosis Type 1 Alternative Splicing Is a Key Regulator of Ras Signaling in Neurons

“…Though Nf1 is widely expressed, it is most abundant in neurons, Schwann cells, and oligodendrocytes, and it plays important roles in the nervous system (14)(15)(16)(17)(18)(19). The phenotypes of mouse models suggest that mouse Nf1, whose amino acid sequence is Ͼ98% conserved with that of human Nf1, has important functions in nervous system development (20).…”

Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues.

“…The developmental expression pattern of NF1 protein has been analyzed in the rat (Daston and Ratner 1992) and the mouse (Huynh et al 1994). Neurofibromin is uniformly distributed throughout embryonic days 8-11.…”

Region-specific astrogliosis in brains of mice heterozygous for mutations in the neurofibromatosis type 1 (Nf1) tumor suppressor

“…Aliquots containing 0.3, 1, 3, and 10 μg of protein were diluted in Laemmli buffer and loaded onto 12% polyacrylamide gels. Electrophoresis and Western blot analysis was performed as previously described [8]. Polyclonal antibody to GFAP (rabbit, Dako-Catalog #Z334) was used at a dilution of 1:1000 for western analysis of tissue extracts.…”