Abstract
THE receptor erbB2/neu is a member of the epidermal growth factor receptor (EGFR or erbB) family that also includes erbB3 and erbB41. Amplification of the erbB2/neu gene is found in many cancer types and its overexpression is correlated with a poor prognosis for breast and ovarian cancer patients2. Investigation of the biology of erbB2 led to the identification of a family of ligands termed neuregulins which included the neu-differentiation factors3,4, the heregulins5, a ligand with acetylcholine-receptor-inducing activity6 and glial growth factor7. Several lines of evidence suggest that heterodimerization of erbB2 with other erbB receptors is required for neuregulin signalling1. Here we investigate the developmental role of erbB2 in mammalian development in mice carrying an erbB2 null allele. We find that mutant embryos die before Ell, probably as a result of dysfunctions associated with a lack of cardiac trabeculae. Development of cranial neural-crest-derived sensory ganglia was markedly affected. Dil retrograde tracing revealed that the development of motor nerves was also compromised. Our results demonstrate the importance of erbB2 in neural and cardiac development.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
204,58 € per year
only 4,01 € per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Carraway, K. L. III & Burden, S. J. Curr. Opin. Neurobiol. 5, 1–7 (1995).
Hynes, N. E. & Stern, D. F. Biochem. biophys. Acta 1198, 165–184 (1994).
Peles, E. et al. Cell 69, 205–216 (1992).
Wen, D. et al. Cell 69, 559–572 (1992).
Holmes, W. E. et al. Science 256, 1205–1210 (1992).
Falls, D. L., Rosen, K. M., Corfas, G., Lane, W. S. & Fischbach, G. D. Cell 72, 801–815 (1993).
Marchionni, M. A. et al. Nature 362, 312–318 (1993).
Kokai, Y., Cohen, J. A., Drebin, J. A. & Greene, M. I. Proc. natn. Acad. Sci. U.SA 84, 8498–8501 (1987).
Press, M. F., Cordon-Cardo, C. & Slamon, D. J. Oncogene 5, 953–962 (1990).
Orr-Urtreger, A. et al. Proc. natn. Acad. Sci. U.S.A. 90, 1867–1871 (1993).
Meyer, D. & Birchmeier, C. Proc. natn. Acad. Sci. U.S.A. 94, 1064–1068 (1994).
Shah, N. M., Marchionni, M. A., Isaacs, I., Stroobant, P. & Andersen, D. J. Cell 77, 349–360 (1994).
Corfas, G., Rosen, K. M., Aratake, H., Krauss, R. & Fischbach, G. D. Neuron 14, 103–115 (1995).
Ho, W.-H., Armanini, M. P., Nuijens, A., Phillips, H. S. & Osheroff, P. L. J. biol. Chem. 270, 14523–14532 (1995).
D'Amico-Martel, A. & Noden, D. M. Am. J. Anat. 166, 445–468 (1983).
Le Douarin, N. M. & Smith, J. A. Rev. Cell Biol. 4, 375–404 (1988).
Lumsden, A. & Keynes, R. Nature 337, 424–428 (1989).
Lumsden, A., Sprawson, N. & Graham, A. Development 113, 1281–1291 (1991).
Moody, S. A. & Heaton, M. J. comp. Neurol. 213, 327–343 (1983).
Moody, S. A. & Heaton, M. B. J. comp. Neurol. 213, 344–349 (1983).
Simon, H. & Lumsden, A. Neuron 11, 209–220 (1993).
Vartanian, T., Corfas, G., Li, Y., Fischbach, G. D. & Stefansson, K. Proc. natn. Acad. Sci. U.S.A. 91, 11626–11630 (1994).
Pinkas-Kramarski, R. et al. Proc. natn. Acad. Sci. U.S.A. 91, 9387–9391 (1994).
Dong, Z. et al. Neuron 15, 589–596 (1995).
Weston, J. A. & Butler, S. L. Devl Biol. 14, 246–266 (1966).
Nichols, D. H. J. Embryol. exp. Morph. 64, 105–120 (1981).
Meyer, D. & Birchmeier, C. Nature 378, 394–398 (1995).
Gassmann, M. et al. Nature 378, 390–394 (1995).
White, M. R.-A. & Hung, M.-C. Oncogene 7, 677–683 (1992).
Lee, K. F. et al. Cell 69, 737–749 (1992).
Easter, S. S. Jr, Ross, L. S. & Frankfurther, A. J. Neurosci. 13, 285–299 (1993).
Dent, J. A., Polson, A. G. & Klymkowsky, M. W. Development 105, 61–74 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lee, KF., Simon, H., Chen, H. et al. Requirement for neuregulin receptor erbB2 in neural and cardiac development. Nature 378, 394–398 (1995). https://doi.org/10.1038/378394a0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/378394a0


