Advertisement
JOURNAL ARTICLES
The Hox11 gene is essential for cell survival during spleen development
T.N. Dear, W.H. Colledge, M.B. Carlton, I. Lavenir, T. Larson, A.J. Smith, A.J. Warren, M.J. Evans, M.V. Sofroniew, T.H. Rabbitts
Development 1995 121: 2909-2915;

Summary

The HOX11 homeobox gene was identified via the translocation t(10;14) in T cell leukaemia. To determine the function of this gene in mice, null mutations were made using homologous recombination in ES cells to incorporate lacZ into the hox11 transcription unit. Production of beta-galactosidase from the recombinant hox11 allele in +/− mutants allowed identification of sites of hox11 expression which included the developing spleen. Newborn hox11 −/− mice exhibit asplenia. Spleen formation commences normally at E11.5 in hox11 −/− mutant embryos but the spleen anlage undergoes rapid and complete resorption between E12.5 and E13.5. Dying spleen cells exhibit molecular features of apoptosis, suggesting that programmed cell death is initiated at this stage of organ development in the absence of hox11 protein. Thus hox11 is not required to initiate spleen development but is essential for the survival of splenic precursors during organogenesis. This function for hox11 suggests that enhanced cell survival may result from the t(10;14) which activates HOX11 in T cell leukaemias, further strengthening the association between oncogene-induced cell survival and tumorigenesis.

Reference

    1. Allen N. D.,
    2. Cran D. G.,
    3. Barton S. C.,
    4. Hettle S.,
    5. Reik W.,
    6. Surani M. A.
    (1988) Transgenes as probes for active chromosomal domains in mouse development. Nature 333, 852–855
    OpenUrlCrossRefPubMed
    1. Boehm T.,
    2. Mengle-Gaw L.,
    3. Kees U. R.,
    4. Spurr N.,
    5. Lavenir I.,
    6. Forster A.,
    7. Rabbitts T. H.
    (1989) Alternating purine- pyrimidine tracts may promote chromosomal translocations seen in a variety of human lymphoid tumours. EMBO J 8, 2621–2631
    OpenUrlPubMedWeb of Science
    1. Dear T. N.,
    2. Sanchez-Garcia I.,
    3. Rabbitts T. H.
    (1993) The HOX11 gene encodes a DNA-binding nuclear transcription factor belonging to a distinct family of homeobox genes. Proc. Natl. Acad. Sci. USA 90, 4431–4435
    OpenUrlAbstract/FREE Full Text
    1. Dube I. D.,
    2. Kamel-Reid S.,
    3. Yuan C. C.,
    4. Lu M.,
    5. Wu X.,
    6. Corpus G.,
    7. Raimondi S. C.,
    8. Crist W. M.,
    9. Carroll A. J.,
    10. Minowada J.,
    11. Baker J. B.
    (1991) A novel human homeobox gene lies at the chromosome 10 breakpoint in lymphoid neoplasias with chromosomal translocation t(10;14). Blood 78, 2996–3003
    OpenUrlAbstract/FREE Full Text
    1. Hatano M.,
    2. Roberts C. W. M.,
    3. Minden M.,
    4. Crist W. M.,
    5. Korsmeyer S. J.
    (1991) Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukaemia. Science 253, 79–82
    OpenUrlAbstract/FREE Full Text
    1. Hockenberry D. M.,
    2. Oitval Z. N.,
    3. Yin X.-M.,
    4. Milliman C. L.,
    5. Korsmeyer S. J.
    (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75, 241–251
    OpenUrlCrossRefPubMedWeb of Science
    1. Kane D. J.,
    2. Sarafian T. A.,
    3. Anton R.,
    4. Hahn H.,
    5. Gralla E. B.,
    6. Valentine J. S.,
    7. Ord T.,
    8. Bredesen D. E.
    (1993) Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262, 1274–1277
    OpenUrlAbstract/FREE Full Text
    1. Kennedy M. A.,
    2. Gonzalez-Sarmiento R.,
    3. Kees U. R.,
    4. Lampert F.,
    5. Dear N.,
    6. Boehm T.,
    7. Rabbitts T. H.
    (1991) HOX11, a homeobox-containing T-cell oncogene on human chromosome 10q24. Proc. Natl. Acad. Sci. USA 88, 8900–8904
    OpenUrlAbstract/FREE Full Text
    1. Kerr J. F. R.,
    2. Wyllie A. H.,
    3. Currie A. R.
    (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257
    OpenUrlPubMedWeb of Science
    1. Krumlauf R.
    (1994) Hox genes in vertebrate development. Cell 78, 191–201
    OpenUrlCrossRefPubMedWeb of Science
    1. Lu M.,
    2. Gong Z.,
    3. Shen W.,
    4. Ho A. D.
    (1991) The tcl-3 proto-oncogene altered by chromosomal translocation in T-cell leukaemia codes for a homeobox protein. EMBO J 10, 2905–2910
    OpenUrlPubMedWeb of Science
    1. Lu M.,
    2. Zhang N.,
    3. Ho A. D.
    (1992) Genomic organisation of the putative human homeobox proto-oncogene HOX-11 (TCL-3) and its endogenous expression in T cells. Oncogene 7, 1325–1330
    OpenUrlPubMedWeb of Science
    1. McDonnell T. J.,
    2. Deane N.,
    3. Platt F. M.,
    4. Nunez G.,
    5. Jaeger U.,
    6. McKearn J. P.,
    7. Korsmeyer S. J.
    (1989) bcl2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell 57, 79–88
    OpenUrlCrossRefPubMedWeb of Science
    1. McDonnell T. J.,
    2. Korsmeyer S. J.
    (1991) Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18). Nature 349, 254–256
    OpenUrlCrossRefPubMed
    1. Rabbitts T. H.
    (1994) Chromosomal translocations in human cancer. Nature 372, 143–149
    OpenUrlCrossRefPubMed
    1. Rabbitts T. H.,
    2. Forster A.,
    3. Larson R.,
    4. Nathan P.
    (1993) Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nature Genetics 4, 175–180
    OpenUrlCrossRefPubMedWeb of Science
    1. Raff M. C.
    (1992) Social controls on cell survival and cell death. Nature 356, 397–400
    OpenUrlCrossRefPubMed
    1. Raju K.,
    2. Tang S.,
    3. Dube I. D.,
    4. Kamel-Reid S.,
    5. Bryce D. M.,
    6. Breitman M. L.
    (1993) Characterisation and developmental expression of Tlx-1, a murine homolog of HOX11. Mech. Develop 44, 51–64
    OpenUrlCrossRefPubMedWeb of Science
    1. Roberts C. W. M.,
    2. Shutter J. R.,
    3. Korsmeyer S. J.
    (1994) Hox11 controls the genesis of the spleen. Nature 368, 747–749
    OpenUrlCrossRefPubMed
    1. Savill J.,
    2. Fadok V.,
    3. Henson P.,
    4. Haslett C.
    (1993) Phagocyte recognition of cells undergoing apoptosis. Immunol. Today 14, 131–136
    OpenUrlCrossRefPubMedWeb of Science
    1. Sentman C. L.,
    2. Shutter J. R.,
    3. Hockenberry D.,
    4. Kanagawa O.,
    5. Korsmeyer S. J.
    (1991) bcl-2 inhibits nultiple forms of apoptosis but not negative selection in thymocytes. Cell 67, 879–888
    OpenUrlCrossRefPubMedWeb of Science
    1. Strasser A.,
    2. Harris A. W.,
    3. Bath M. L.,
    4. Cory S.
    (1990) Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature 348, 331–333
    OpenUrlCrossRefPubMed
    1. Strasser A.,
    2. Harris A. W.,
    3. Cory S.
    (1991) bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67, 889–899
    OpenUrlCrossRefPubMedWeb of Science
    1. Thomas K. R.,
    2. Capecchi M. R.
    (1987) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51, 503–512
    OpenUrlCrossRefPubMedWeb of Science
    1. Warren A. J.,
    2. Colledge W. H.,
    3. Carlton M. B. L.,
    4. Evans M. J.,
    5. Smith A. J. H.,
    6. Rabbitts T. H.
    (1994) The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development. Cell 78, 45–58
    OpenUrlCrossRefPubMedWeb of Science
    1. Wilsman J. H.,
    2. Jonker R. R.,
    3. Keijer R.,
    4. vande Velde C. J.,
    5. Cornelisse C. J.,
    6. van Dierendonck J.
    (1993) A new method to detect apoptosis in parafin sections: in situ end-labelling of fragmented DNA. J. Histochem. Cytochem 41, 7–12
    OpenUrlAbstract/FREE Full Text
    1. Wyllie A. H.,
    2. Morris R. G.,
    3. Smith A. L.,
    4. Dunlop D.
    (1984) Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macrolecular synthesis. J. Path 142, 67–77
    OpenUrlCrossRefPubMedWeb of Science
    1. Zutter M.,
    2. Hockett R. D.,
    3. Roberts C. W. M.,
    4. McGuire E. A.,
    5. Bloomstone J.,
    6. Morton C. C.,
    7. Deaven L. L.,
    8. Crist W. M.,
    9. Carroll A. J.,
    10. Korsmeyer S. J.
    (1990) The t(10;14)(q24;q11) of T-cell acute lymphoblastic leukemia juxtaposes theT-cell receptor with TCL3, a conserved and activated locus at 10q24. Proc. Natl. Acad. Sci. USA 87, 3161–3165
    OpenUrlAbstract/FREE Full Text
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The Hox11 gene is essential for cell survival during spleen development
T.N. Dear, W.H. Colledge, M.B. Carlton, I. Lavenir, T. Larson, A.J. Smith, A.J. Warren, M.J. Evans, M.V. Sofroniew, T.H. Rabbitts
Development 1995 121: 2909-2915;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

The Node is looking for a new Community Manager!

If you're interested in science communication, publishing and the developmental biology community, we're hiring for a new Community Manager for our community site, the Node.

The position is an exciting opportunity to develop an already successful and well-known site, engaging with the academic, publishing and online communities. Find out more and how to apply.

Upcoming special issue: call for papers

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

The special issue welcomes Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

The people behind the papers - Clément Dubois, Shivam Gupta, Andrew Mugler and Marie-Anne Félix

A new paper investigates the robustness of neuroblast migration in the C. elegans larva in the face of both genetic and environmental variation. In an interview, the paper's four authors tell us more about the story.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Every talk is recorded and since launching in August last year, the series has clocked up almost 10k views on YouTube.

Here, Swann Floc'hlay discusses her work modelling dorsal-ventral axis specification in the sea urchin embryo.

Save your spot at our next session:

14 April
Time: 17:00 BST
Chaired by: François Guillemot

12 May
Time: TBC
Chaired by: Paola Arlotta

Join our mailing list to receive news and updates on the series.