Skip to main content
SpringerLink
Log in

Analysis of the sequence and embryonic expression of chicken neurofibromin mRNA

  • Original Articles
  • Published:
Molecular and Chemical Neuropathology

Abstract

Neurofibromatosis type 1 (NF1) is a common inherited disorder that primarily affects tissues derived from the neural crest. Recent identification and characterization of the human NF1 gene has revealed that it encodes a protein (now called neurofibromin) that is similar in sequence to theras-GTPase activator protein (orras-GAP), suggesting that neurofibromin may be a component of cellular signal transduction pathways regulating cellular proliferation and/or differentiation.

To initiate investigations on the role of the NF1 gene product in embryonic development, we have isolated a partial cDNA for chicken neurofibromin. Sequence analysis reveals that the predicted amino acid sequence is highly conserved between chick and human. The chicken cDNA hybridizes to a 12.5-kb transcript on RNA blots, a mol wt similar to that reported for the human and murine mRNAs. Ribonuclease protection assays indicate that NF1 mRNA is expressed in a variety of tissues in the chick embryo; this is confirmed byin situ hybridization analysis. NF1 mRNA expression is detectable as early as embryonic stage 18 in the neural plate. This pattern of expression may suggest a role for neurofibromin during normal development, including that of the nervous system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baizer L., Stocker K., Alkan S. A., and Ciment G. (1990) Chicken growth-associated protein-(GAP)-43: Primary structure and regulated expression of mRNA during embryogenesis.Mol. Brain Res. 7, 61–68.

    Article  PubMed  CAS  Google Scholar 

  • Ballester R., Marchuk D., Boguski M., Saulino A., Letcher R., Wigler M., and Collins F. (1990) The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins.Cell 63, 851–859.

    Article  PubMed  CAS  Google Scholar 

  • Buchberg A. M., Cleveland L. S., Jenkins N. A., and Copeland N. G. (1990) Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway.Nature 347, 291–294.

    Article  PubMed  CAS  Google Scholar 

  • Cawthon R. M., Weiss R., Xu G., Viskochil D., Culver M., Stevens J., Robertson M., Dunn D., Gesteland R., O’Connell P., and White R. (1990) A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations.Cell 62, 193–201.

    Article  PubMed  CAS  Google Scholar 

  • Chomczynski P. and Sacchi N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.Anal. Biochem. 162, 156–159.

    Article  PubMed  CAS  Google Scholar 

  • Ciment G., Glimelius B., Nelson D., and Weston J. A. (1986) Reversal of a developmental restriction in neural crest-derived cells of avian embryos by a phorbol ester drug.Dev. Biol. 118, 392–398.

    Article  PubMed  CAS  Google Scholar 

  • Ciment G. and Weston J. A. (1982) Early appearance in neural crest and crest-derived cells of an antigenic determinant present in avian neurons.Dev. Biol. 93, 355–367.

    Article  PubMed  CAS  Google Scholar 

  • Daston M. M., Scrable H., Nordlund M., Sturbaum A. K., Nissen L. M., and Ratner N. (1992) The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes.Neuron 8, 415–428.

    Article  PubMed  CAS  Google Scholar 

  • Feinberg A. B. and Vogelstein B. (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.Anal. Biochem. 132, 6–11.

    Article  PubMed  CAS  Google Scholar 

  • Hall A. (1990) ras and GAP — who’s controlling whom?Cell 61, 921–923.

    Article  PubMed  CAS  Google Scholar 

  • Hamburger V. and Hamilton H. L. (1951) A series of normal stages in the development of the chick embryo.J. Morphol. 88, 49–67.

    Article  Google Scholar 

  • Kusukawa N., Vemori T., Aseda K., and Kato I. (1990) Rapid and reliable protocol for direct sequencing of material amplified by the polymerase chain reaction.Bio Techniques 9, 66–92.

    CAS  Google Scholar 

  • LeDouarin N. M. (1982)The Neural Crest. Cambridge University Press, New York.

    Google Scholar 

  • LeDouarin N. M. (1986) Cell line segregation during nervous system ontogeny.Science 231, 1515–1522.

    Article  CAS  Google Scholar 

  • Marchuk D. A., Saulino A. M., Tavakkol R., Swaroop M., Wallace M. R., Andersen L. B., Mitchell A. L., Gutman D. H., Boguski M., and Collins F. S. (1991) cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product.Genomics 11, 931–940.

    Article  PubMed  CAS  Google Scholar 

  • Martin G. A., Viskochil D., Bollag G., McCabe P. C., Crosier W. J., Haubruck H., Conroy L., Clark R., O’Connell P., Cawthon R. M., Innis M. A., and McCormick F. (1990) The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21.Cell 63, 843–849.

    Article  PubMed  CAS  Google Scholar 

  • McCormick F. (1989) ras GTPase activating protein: signal transmitter and signal terminator.Cell 56, 5–8.

    Article  PubMed  CAS  Google Scholar 

  • Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., and Green M. R. (1984) Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage Sp6 promoter.Nucleic. Acids Res. 12, 7035–7056.

    Article  PubMed  CAS  Google Scholar 

  • Orkin S. H. (1986) Reversed genetics.Cell 47, 845–848.

    Article  PubMed  CAS  Google Scholar 

  • Riccardi V. M. and Eichner J. E. (1986)Neurofibromatosis: Phenotype, Natural History, and Pathogenesis. Johns Hopkins University Press, Baltimore, MD.

    Google Scholar 

  • Sambrook J., Fritsch E. F., Maniatis T. (1989)Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

    Google Scholar 

  • Sears R. and Ciment G. (1988) Changes in the migratory proerties of neural crest and early neural crest-derived cells in vivo following treatment with a phorbol ester drug.Dev. Biol. 130, 133–143.

    Article  PubMed  CAS  Google Scholar 

  • Stocker K. M., Sherman L., Rees S., and Ciment G. (1991) Basic FGF and TGF β-1 influence commitment to melanogenesis in neural crest-derived cells of avian embryos.Development 111 635–645.

    PubMed  CAS  Google Scholar 

  • Stumpf D. A., Alksne J. F., Annegers J. F., Brown S. S., Conneally P. M., Housman D., Leppert M., Miller J. P., Moss M. L., Pileggi A. J., Rapin I., Strohman R. C., Swanson L. W., and Zimmerman A. (1987) Neurofibromatosis.Arch. Neurol. 45, 575–578.

    Google Scholar 

  • Tanaka K., Matsumoto S., and Toh-e A. (1989) IRA1, an inhibitory regulator of the RAS/cyclic AMP pathway in saccharomyces cerevisiae.Mol. Cell. Biol. 9, 757–768.

    PubMed  CAS  Google Scholar 

  • Tanaka K., Nakafuku M., Satoh T., Marshall M. S., Gibbs J. B., Matsumoto K., Kaziro Y., and Toh-e A. (1990)S. cerevisiae genes IRA1 and IRA2 encode proteins that may be functionally equivalent to mammalian ras GTPase-activating protein.Cell 60, 803–807.

    Article  PubMed  CAS  Google Scholar 

  • Trahey M. and McCormick F. (1987) A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants.Science 238, 542–545.

    Article  PubMed  CAS  Google Scholar 

  • Tucker G. C., Aoyama H., Lipinski M., Turz T., and Thiery J. P. (1984) Identical reactivity of monoclonal antibodies HNK-1 and NC-1: Conservation in vertebrates on cells derived from neural primordium and on some leukocytes.Cell Differ. 14, 223–230.

    Article  PubMed  CAS  Google Scholar 

  • Vincent M. and Thiery J. P. (1984) A cell surface marker for neural crest and placodal cells: Further evolution of the peripheral and central nervous system.Dev. Biol. 103, 468–481.

    Article  PubMed  CAS  Google Scholar 

  • Viskochil D., Buchberg A. M., Xu G., Cawthon R. M., Stevens J., Wolff R. K., Culver M., Carey J. C., Copeland N. G., Jenkins N. A., White R., and O’Connell P. (1990) Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus.Cell 62, 187–192.

    Article  PubMed  CAS  Google Scholar 

  • Wallace M. R., Marchuk D. A., Andersen L. B., Letcher R., Odeh H. M., Saulino A. M., Fountain J. W., Brereton A., Nicholson J., Mitchell A. L., Brownstein B. H., and Collins F. S. (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients.Science 249, 181–186.

    Article  PubMed  CAS  Google Scholar 

  • White R., Viskochil D., and O’Connell P. (1991) Identification and characterization of the gene for neurofibromatosis type 1.Curr. Opinion Neurobiol. 1, 462–467.

    Article  CAS  Google Scholar 

  • Xu G., O’Connell P., Viskochil D., Cawthon R., Robertson M., Culver M., Dunn D., Stevens J., Gesteland R., White R., and Weiss R. (1990a) The neurofibromatosis type 1 gene encodes a protein related to GAP.Cell 62, 599–608.

    Article  PubMed  CAS  Google Scholar 

  • Xu G., Lin B., Tanaka K., Dunn D., Wood D., Gesteland R., White R., Weiss R., and Tamanoi F. (1990b) The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants ofS. cerevisiae.Cell 63, 835–841.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. R. S. Dow Neurological Sciences Institute, Good Samaritan Hospital and Medical Center, Oregon Health Sciences University, 97209, Portland, OR

    Gwen L. Schafer & Lawrence Baizer

  2. Department of Cell Biology and Anatomy, Oregon Health Sciences University, 97209, Portland, OR

    Gary Ciment & Kate M. Stocker

Authors
  1. Gwen L. Schafer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gary Ciment
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kate M. Stocker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lawrence Baizer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schafer, G.L., Ciment, G., Stocker, K.M. et al. Analysis of the sequence and embryonic expression of chicken neurofibromin mRNA. Molecular and Chemical Neuropathology 18, 267–278 (1993). https://doi.org/10.1007/BF03160119

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03160119

Index Entries

Search

Navigation