An activated notch receptor blocks cell-fate commitment in the developing drosophila eye

An activated notch receptor blocks cell-fate commitment in the developing drosophila eye

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ABSTRACT THE _Notch_ locus of _Drosophila melanogaster_ encodes a 2,703-amino-acid transmembrane protein required for a variety of developmental processes, including neurogenesis, oogenesis and ommatidial assembly1,2. The Notch protein contains a large extracellular domain of 36 epidermal growth factor-like repeats as well as three Notch/Lin-12 repeats and an intracellular domain with 6 CdclO/ ankyrin repeats, motifs that are highly conserved in several vertebrate Notch homologues3–9. Truncation of the extracellular domain of the _Drosophila_ Notch protein produces an activated receptor, as judged by its ability to cause phenotypes similar to gain-of-function alleles or duplications of the _Notch_ locus10. Equivalent truncations of vertebrate Notch-related proteins have been associated with malignant neoplasms and other developmental abnormalities8,11–13. We present here an analysis of activated Notch function at single-cell resolution in the _Drosophila_ compound eye. We find that overexpression of full-length Notch in defined cell types has no apparent effects but that overexpression of activated Notch in the same cells transiently blocks their proper cell-fate commitment, causing them either to adopt incorrect cell fates or to differentiate incompletely. Moreover, an activated Notch protein lacking the transmembrane domain is translocated to the nucleus, raising the possibility that Notch may participate directly in nuclear events. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print issues and online access $199.00 per year only $3.90 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS A NON-CANONICAL RAF FUNCTION IS REQUIRED FOR DORSAL–VENTRAL PATTERNING DURING _DROSOPHILA_ EMBRYOGENESIS Article Open access 10 May 2022 SYNERGISTIC ACTIVATION BY GLASS AND POINTED PROMOTES NEURONAL IDENTITY IN THE _DROSOPHILA_ EYE DISC Article Open access 17 August 2024 THE _NTAN1_ GENE IS EXPRESSED IN PERINEURAL GLIA AND NEURONS OF ADULT _DROSOPHILA_ Article Open access 30 August 2022 REFERENCES * Artavanis-Tsakonas, S. & Simpson, P. _Trends Genet._ 7, 403–408 (1991). Article  CAS  PubMed  Google Scholar  * Greenwald, I. & Rubin, G. M. _Cell_ 68, 271–281 (1992). Article  CAS  PubMed  Google Scholar  * Wharton, K. A., Johansen, K. M., Xu, T. & Artavanis-Tsakonas, S. _Cell_ 43, 567–581 (1985). Article  CAS  PubMed  Google Scholar  * Kidd, S., Kelley, M. R. & Young, M. W. _Molec. cell. Biol._ 6, 3094–3108 (1986). Article  CAS  PubMed  PubMed Central  Google Scholar  * Coffman, C., Harris, W. & Kintner, C. _Science_ 249, 1438–1441 (1990). Article  ADS  CAS  PubMed  Google Scholar  * Weinmaster, G., Roberts, V. J. & Lemke, G. _Development_ 113, 199–205 (1991). CAS  PubMed  Google Scholar  * Franco del Amo, F. _et al._ _Development_ 115, 737–744 (1992). CAS  Google Scholar  * Ellisen, L. W. _et al._ _Cell_ 66, 649–661 (1991). Article  CAS  PubMed  Google Scholar  * Stifani, S., Blaumueller, C. M., Redhead, N. J., Hill, R. E. & Artavanis-Tsakonas, S. _Nature Genet._ 2, 119–127 (1992). Article  CAS  PubMed  Google Scholar  * Rebay, I., Fehon, R. G. & Artavanis-Tsakonas, S. _Cell_ 74, 319–329 (1993). Article  CAS  PubMed  Google Scholar  * Robbins, J., Blondel, B. J., Gallahan, D. & Callahan, R. _J. Virol._ 66, 2594–2599 (1992). CAS  PubMed  PubMed Central  Google Scholar  * Jhappan, C. _et al._ _Genes Dev._ 6, 345–355 (1992). Article  CAS  PubMed  Google Scholar  * Coffman, C. R., Skoglund, P., Harris, W. A. & Kintner, C. R. _Cell_ 73, 659–671 (1993). Article  CAS  PubMed  Google Scholar  * Tomlinson, A., Bowtell, D. D. L., Hafen, E. & Rubin, G. M. _Cell_ 51, 143–150 (1987). Article  CAS  PubMed  Google Scholar  * Bowtell, D. D. L., Kimmel, B. E., Simon, M. A. & Rubin, G. M. _Proc. natn. Acad. Sci. U.S.A._ 86, 6245–6249 (1989). Article  ADS  CAS  Google Scholar  * Fehon, R. G., Johansen, K., Rebay, I. & Artavanis-Tsakonas, S. _J. Cell Biol._ 113, 657–669 (1991). Article  CAS  PubMed  Google Scholar  * Heitzler, P. & Simpson, P. _Cell_ 64, 1083–1092 (1991). Article  CAS  PubMed  Google Scholar  * Mlodzik, M., Hiromi, Y., Weber, U., Goodman, C. S. & Rubin, G. M. _Cell_ 60, 211–224 (1990). Article  CAS  PubMed  Google Scholar  * Heberlein, U., Mlodzik, M. & Rubin, G. M. _Development_ 112, 703–712 (1991). CAS  PubMed  Google Scholar  * Rubin, G. M. _Trends Genet._ 7, 372–377 (1991). Article  CAS  PubMed  Google Scholar  * Tomlinson, A. & Ready, D. F. _Devl Biol._ 123, 264–275 (1987). Article  CAS  Google Scholar  * Reinke, R. & Zipursky, S. L. _Cell_ 55, 321–330 (1988). Article  CAS  PubMed  Google Scholar  * Carthew, R. W. & Rubin, G. M. _Cell_ 63, 561–577 (1990). Article  CAS  PubMed  Google Scholar  * Smoller, D. _et al._ _Genes Dev._ 4, 1688–1700 (1990). Article  CAS  PubMed  Google Scholar  * Delidakis, C., Preiss, A., Hartley, D. A. & Artavanis-Tsakonas, S. _Genetics_ 129, 803–823 (1991). CAS  PubMed  PubMed Central  Google Scholar  * Bier, E., Ackerman, L., Barbel, S., Jan, L. & Jan, Y. N. _Science_ 240, 913–916 (1988). Article  ADS  CAS  PubMed  Google Scholar  * Robinow, S. & White, K. _J. Neurobiol._ 22, 443–461 (1991). Article  CAS  PubMed  Google Scholar  * Fortini, M. E., Simon, M. A. & Rubin, G. M. _Nature_ 355, 559–561 (1992). Article  ADS  CAS  PubMed  Google Scholar  * Fortini, M. E. & Rubin, G. M. _Genes Dev._ 4, 444–463 (1990). Article  CAS  PubMed  Google Scholar  * Gaul, U., Mardon, G. & Rubin, G. M. _Cell_ 68, 1007–1019 (1992). Article  CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Departments of Cell Biology and Biology, and Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, 06536, USA Mark E. Fortini, Ilaria Rebay, Laurent A. Caron & Spyros Artavanis-Tsakonas Authors * Mark E. Fortini View author publications You can also search for this author inPubMed Google Scholar * Ilaria Rebay View author publications You can also search for this author inPubMed Google Scholar * Laurent A. Caron View author publications You can also search for this author inPubMed Google Scholar * Spyros Artavanis-Tsakonas View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Fortini, M., Rebay, I., Caron, L. _et al._ An activated Notch receptor blocks cell-fate commitment in the developing _Drosophila_ eye. _Nature_ 365, 555–557 (1993). https://doi.org/10.1038/365555a0 Download citation * Received: 19 May 1993 * Accepted: 24 August 1993 * Issue Date: 07 October 1993 * DOI: https://doi.org/10.1038/365555a0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

ABSTRACT THE _Notch_ locus of _Drosophila melanogaster_ encodes a 2,703-amino-acid transmembrane protein required for a variety of developmental processes, including neurogenesis, oogenesis


and ommatidial assembly1,2. The Notch protein contains a large extracellular domain of 36 epidermal growth factor-like repeats as well as three Notch/Lin-12 repeats and an intracellular


domain with 6 CdclO/ ankyrin repeats, motifs that are highly conserved in several vertebrate Notch homologues3–9. Truncation of the extracellular domain of the _Drosophila_ Notch protein


produces an activated receptor, as judged by its ability to cause phenotypes similar to gain-of-function alleles or duplications of the _Notch_ locus10. Equivalent truncations of vertebrate


Notch-related proteins have been associated with malignant neoplasms and other developmental abnormalities8,11–13. We present here an analysis of activated Notch function at single-cell


resolution in the _Drosophila_ compound eye. We find that overexpression of full-length Notch in defined cell types has no apparent effects but that overexpression of activated Notch in the


same cells transiently blocks their proper cell-fate commitment, causing them either to adopt incorrect cell fates or to differentiate incompletely. Moreover, an activated Notch protein


lacking the transmembrane domain is translocated to the nucleus, raising the possibility that Notch may participate directly in nuclear events. Access through your institution Buy or


subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print issues and online


access $199.00 per year only $3.90 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which


are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS


A NON-CANONICAL RAF FUNCTION IS REQUIRED FOR DORSAL–VENTRAL PATTERNING DURING _DROSOPHILA_ EMBRYOGENESIS Article Open access 10 May 2022 SYNERGISTIC ACTIVATION BY GLASS AND POINTED PROMOTES


NEURONAL IDENTITY IN THE _DROSOPHILA_ EYE DISC Article Open access 17 August 2024 THE _NTAN1_ GENE IS EXPRESSED IN PERINEURAL GLIA AND NEURONS OF ADULT _DROSOPHILA_ Article Open access 30


August 2022 REFERENCES * Artavanis-Tsakonas, S. & Simpson, P. _Trends Genet._ 7, 403–408 (1991). Article  CAS  PubMed  Google Scholar  * Greenwald, I. & Rubin, G. M. _Cell_ 68,


271–281 (1992). Article  CAS  PubMed  Google Scholar  * Wharton, K. A., Johansen, K. M., Xu, T. & Artavanis-Tsakonas, S. _Cell_ 43, 567–581 (1985). Article  CAS  PubMed  Google Scholar 


* Kidd, S., Kelley, M. R. & Young, M. W. _Molec. cell. Biol._ 6, 3094–3108 (1986). Article  CAS  PubMed  PubMed Central  Google Scholar  * Coffman, C., Harris, W. & Kintner, C.


_Science_ 249, 1438–1441 (1990). Article  ADS  CAS  PubMed  Google Scholar  * Weinmaster, G., Roberts, V. J. & Lemke, G. _Development_ 113, 199–205 (1991). CAS  PubMed  Google Scholar  *


Franco del Amo, F. _et al._ _Development_ 115, 737–744 (1992). CAS  Google Scholar  * Ellisen, L. W. _et al._ _Cell_ 66, 649–661 (1991). Article  CAS  PubMed  Google Scholar  * Stifani, S.,


Blaumueller, C. M., Redhead, N. J., Hill, R. E. & Artavanis-Tsakonas, S. _Nature Genet._ 2, 119–127 (1992). Article  CAS  PubMed  Google Scholar  * Rebay, I., Fehon, R. G. &


Artavanis-Tsakonas, S. _Cell_ 74, 319–329 (1993). Article  CAS  PubMed  Google Scholar  * Robbins, J., Blondel, B. J., Gallahan, D. & Callahan, R. _J. Virol._ 66, 2594–2599 (1992). CAS 


PubMed  PubMed Central  Google Scholar  * Jhappan, C. _et al._ _Genes Dev._ 6, 345–355 (1992). Article  CAS  PubMed  Google Scholar  * Coffman, C. R., Skoglund, P., Harris, W. A. &


Kintner, C. R. _Cell_ 73, 659–671 (1993). Article  CAS  PubMed  Google Scholar  * Tomlinson, A., Bowtell, D. D. L., Hafen, E. & Rubin, G. M. _Cell_ 51, 143–150 (1987). Article  CAS 


PubMed  Google Scholar  * Bowtell, D. D. L., Kimmel, B. E., Simon, M. A. & Rubin, G. M. _Proc. natn. Acad. Sci. U.S.A._ 86, 6245–6249 (1989). Article  ADS  CAS  Google Scholar  * Fehon,


R. G., Johansen, K., Rebay, I. & Artavanis-Tsakonas, S. _J. Cell Biol._ 113, 657–669 (1991). Article  CAS  PubMed  Google Scholar  * Heitzler, P. & Simpson, P. _Cell_ 64, 1083–1092


(1991). Article  CAS  PubMed  Google Scholar  * Mlodzik, M., Hiromi, Y., Weber, U., Goodman, C. S. & Rubin, G. M. _Cell_ 60, 211–224 (1990). Article  CAS  PubMed  Google Scholar  *


Heberlein, U., Mlodzik, M. & Rubin, G. M. _Development_ 112, 703–712 (1991). CAS  PubMed  Google Scholar  * Rubin, G. M. _Trends Genet._ 7, 372–377 (1991). Article  CAS  PubMed  Google


Scholar  * Tomlinson, A. & Ready, D. F. _Devl Biol._ 123, 264–275 (1987). Article  CAS  Google Scholar  * Reinke, R. & Zipursky, S. L. _Cell_ 55, 321–330 (1988). Article  CAS  PubMed


  Google Scholar  * Carthew, R. W. & Rubin, G. M. _Cell_ 63, 561–577 (1990). Article  CAS  PubMed  Google Scholar  * Smoller, D. _et al._ _Genes Dev._ 4, 1688–1700 (1990). Article  CAS 


PubMed  Google Scholar  * Delidakis, C., Preiss, A., Hartley, D. A. & Artavanis-Tsakonas, S. _Genetics_ 129, 803–823 (1991). CAS  PubMed  PubMed Central  Google Scholar  * Bier, E.,


Ackerman, L., Barbel, S., Jan, L. & Jan, Y. N. _Science_ 240, 913–916 (1988). Article  ADS  CAS  PubMed  Google Scholar  * Robinow, S. & White, K. _J. Neurobiol._ 22, 443–461 (1991).


Article  CAS  PubMed  Google Scholar  * Fortini, M. E., Simon, M. A. & Rubin, G. M. _Nature_ 355, 559–561 (1992). Article  ADS  CAS  PubMed  Google Scholar  * Fortini, M. E. &


Rubin, G. M. _Genes Dev._ 4, 444–463 (1990). Article  CAS  PubMed  Google Scholar  * Gaul, U., Mardon, G. & Rubin, G. M. _Cell_ 68, 1007–1019 (1992). Article  CAS  PubMed  Google Scholar


  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Departments of Cell Biology and Biology, and Howard Hughes Medical Institute, Yale University, New Haven, Connecticut,


06536, USA Mark E. Fortini, Ilaria Rebay, Laurent A. Caron & Spyros Artavanis-Tsakonas Authors * Mark E. Fortini View author publications You can also search for this author inPubMed 


Google Scholar * Ilaria Rebay View author publications You can also search for this author inPubMed Google Scholar * Laurent A. Caron View author publications You can also search for this


author inPubMed Google Scholar * Spyros Artavanis-Tsakonas View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and


permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Fortini, M., Rebay, I., Caron, L. _et al._ An activated Notch receptor blocks cell-fate commitment in the developing _Drosophila_ eye.


_Nature_ 365, 555–557 (1993). https://doi.org/10.1038/365555a0 Download citation * Received: 19 May 1993 * Accepted: 24 August 1993 * Issue Date: 07 October 1993 * DOI:


https://doi.org/10.1038/365555a0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently


available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative