L. Baizer et al., REGULATED EXPRESSION OF THE NEUROFIBROMIN TYPE-I TRANSCRIPT IN THE DEVELOPING CHICKEN BRAIN, Journal of neurochemistry, 61(6), 1993, pp. 2054-2060
Neurofibromatosis type 1 (NF-1) is among the most common inherited dis
eases affecting cells of the central and peripheral nervous systems. A
region of the NF-1 gene is similar in sequence to the ras-GTPase acti
vator protein (ras-GAP), and investigations have confirmed that the NF
-1 gene product (now known as neurofibromin) stimulates ras-GTPase act
ivity in vitro and in vivo. Neurofibromin modulates the ability of ras
proteins to regulate cellular proliferation and/or differentiation, s
uggesting a possible role in normal development. An alternative form o
f the neurofibromin transcript with an additional 63-bp exon inserted
in the GAP-related domain (GRD) has been described recently. To determ
ine whether differential expression of the two forms of neurofibromin
GRD mRNA plays a role in embryonic development, we have isolated and c
haracterized the corresponding chicken cDNA. The predicted amino acid
sequence for the inserted exon is identical between chick and human, a
s are the exon-intron boundaries. RNase protection and RNA-polymerase
chain reaction analyses demonstrate that most tissues express predomin
antly type II mRNA (which contains the insert) throughout embryonic de
velopment. In contrast, whereas type II is the major form in the brain
early in development, expression of the type I transcript (without th
e insert) in this tissue increases dramatically at later times. Analys
is of primary cultures derived from chick embryo brain indicates that
the type I mRNA is enriched in neurons.