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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jan 1;90(1):227–231. doi: 10.1073/pnas.90.1.227

LH-2: a LIM/homeodomain gene expressed in developing lymphocytes and neural cells.

Y Xu 1, M Baldassare 1, P Fisher 1, G Rathbun 1, E M Oltz 1, G D Yancopoulos 1, T M Jessell 1, F W Alt 1
PMCID: PMC45633  PMID: 7678338

Abstract

A screen for early markers of B-lymphocyte differentiation has identified a homeobox gene, denoted LH-2, that has a pattern of expression distinct from that of other related genes. The LH-2 cDNA sequence encodes a polypeptide of 426 amino acids that contains a homeodomain and two repeats of a cysteine-rich domain referred to as a LIM domain. The homeodomain of the LH-2 protein is related to that of other LIM/homeodomain proteins, most strikingly with that of the Drosophila apterous protein. Expression of LH-2 was found in B- and T-lymphoid cell lines. Expression in B-cell lines was highest in lines that represent early stages of differentiation, whereas in T-cell lines there was no clear correlation with the stage of differentiation. In embryonic and adult tissues, the highest level of LH-2 expression was found in discrete regions of the developing central nervous system, primarily in diencephalic and telencephalic structures, and in a subset of lymphoid tissues. The expression pattern and structural characteristics of the LH-2 gene suggest that it encodes a transcriptional regulatory protein involved in the control of cell differentiation in developing lymphoid and neural cell types.

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Selected References

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  1. Blackwell T. K., Alt F. W. Molecular characterization of the lymphoid V(D)J recombination activity. J Biol Chem. 1989 Jun 25;264(18):10327–10330. [PubMed] [Google Scholar]
  2. Boehm T., Foroni L., Kennedy M., Rabbitts T. H. The rhombotin gene belongs to a class of transcriptional regulators with a potential novel protein dimerisation motif. Oncogene. 1990 Jul;5(7):1103–1105. [PubMed] [Google Scholar]
  3. Boehm T., Spillantini M. G., Sofroniew M. V., Surani M. A., Rabbitts T. H. Developmentally regulated and tissue specific expression of mRNAs encoding the two alternative forms of the LIM domain oncogene rhombotin: evidence for thymus expression. Oncogene. 1991 May;6(5):695–703. [PubMed] [Google Scholar]
  4. Cohen B., McGuffin M. E., Pfeifle C., Segal D., Cohen S. M. apterous, a gene required for imaginal disc development in Drosophila encodes a member of the LIM family of developmental regulatory proteins. Genes Dev. 1992 May;6(5):715–729. doi: 10.1101/gad.6.5.715. [DOI] [PubMed] [Google Scholar]
  5. Ericson J., Thor S., Edlund T., Jessell T. M., Yamada T. Early stages of motor neuron differentiation revealed by expression of homeobox gene Islet-1. Science. 1992 Jun 12;256(5063):1555–1560. doi: 10.1126/science.1350865. [DOI] [PubMed] [Google Scholar]
  6. Freyd G., Kim S. K., Horvitz H. R. Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11. Nature. 1990 Apr 26;344(6269):876–879. doi: 10.1038/344876a0. [DOI] [PubMed] [Google Scholar]
  7. Furley A. J., Morton S. B., Manalo D., Karagogeos D., Dodd J., Jessell T. M. The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity. Cell. 1990 Apr 6;61(1):157–170. doi: 10.1016/0092-8674(90)90223-2. [DOI] [PubMed] [Google Scholar]
  8. Havran W. L., Allison J. P. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature. 1988 Sep 29;335(6189):443–445. doi: 10.1038/335443a0. [DOI] [PubMed] [Google Scholar]
  9. Havran W. L., Allison J. P. Origin of Thy-1+ dendritic epidermal cells of adult mice from fetal thymic precursors. Nature. 1990 Mar 1;344(6261):68–70. doi: 10.1038/344068a0. [DOI] [PubMed] [Google Scholar]
  10. Karlsson O., Thor S., Norberg T., Ohlsson H., Edlund T. Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a Cys-His domain. Nature. 1990 Apr 26;344(6269):879–882. doi: 10.1038/344879a0. [DOI] [PubMed] [Google Scholar]
  11. Klar A., Baldassare M., Jessell T. M. F-spondin: a gene expressed at high levels in the floor plate encodes a secreted protein that promotes neural cell adhesion and neurite extension. Cell. 1992 Apr 3;69(1):95–110. doi: 10.1016/0092-8674(92)90121-r. [DOI] [PubMed] [Google Scholar]
  12. Kuziel W. A., Takashima A., Bonyhadi M., Bergstresser P. R., Allison J. P., Tigelaar R. E., Tucker P. W. Regulation of T-cell receptor gamma-chain RNA expression in murine Thy-1+ dendritic epidermal cells. Nature. 1987 Jul 16;328(6127):263–266. doi: 10.1038/328263a0. [DOI] [PubMed] [Google Scholar]
  13. Li P. M., Reichert J., Freyd G., Horvitz H. R., Walsh C. T. The LIM region of a presumptive Caenorhabditis elegans transcription factor is an iron-sulfur- and zinc-containing metallodomain. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9210–9213. doi: 10.1073/pnas.88.20.9210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lillien L. E., Raff M. C. Differentiation signals in the CNS: type-2 astrocyte development in vitro as a model system. Neuron. 1990 Aug;5(2):111–119. doi: 10.1016/0896-6273(90)90301-u. [DOI] [PubMed] [Google Scholar]
  15. McGinnis W., Krumlauf R. Homeobox genes and axial patterning. Cell. 1992 Jan 24;68(2):283–302. doi: 10.1016/0092-8674(92)90471-n. [DOI] [PubMed] [Google Scholar]
  16. McGuire E. A., Hockett R. D., Pollock K. M., Bartholdi M. F., O'Brien S. J., Korsmeyer S. J. The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein. Mol Cell Biol. 1989 May;9(5):2124–2132. doi: 10.1128/mcb.9.5.2124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  18. Porteus M. H., Bulfone A., Ciaranello R. D., Rubenstein J. L. Isolation and characterization of a novel cDNA clone encoding a homeodomain that is developmentally regulated in the ventral forebrain. Neuron. 1991 Aug;7(2):221–229. doi: 10.1016/0896-6273(91)90260-7. [DOI] [PubMed] [Google Scholar]
  19. Price M., Lemaistre M., Pischetola M., Di Lauro R., Duboule D. A mouse gene related to Distal-less shows a restricted expression in the developing forebrain. Nature. 1991 Jun 27;351(6329):748–751. doi: 10.1038/351748a0. [DOI] [PubMed] [Google Scholar]
  20. Rolink A., Melchers F. Molecular and cellular origins of B lymphocyte diversity. Cell. 1991 Sep 20;66(6):1081–1094. doi: 10.1016/0092-8674(91)90032-t. [DOI] [PubMed] [Google Scholar]
  21. Schneuwly S., Kuroiwa A., Baumgartner P., Gehring W. J. Structural organization and sequence of the homeotic gene Antennapedia of Drosophila melanogaster. EMBO J. 1986 Apr;5(4):733–739. doi: 10.1002/j.1460-2075.1986.tb04275.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Short J. M., Fernandez J. M., Sorge J. A., Huse W. D. Lambda ZAP: a bacteriophage lambda expression vector with in vivo excision properties. Nucleic Acids Res. 1988 Aug 11;16(15):7583–7600. doi: 10.1093/nar/16.15.7583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Taira M., Jamrich M., Good P. J., Dawid I. B. The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos. Genes Dev. 1992 Mar;6(3):356–366. doi: 10.1101/gad.6.3.356. [DOI] [PubMed] [Google Scholar]
  24. Tao W., Lai E. Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family, in the developing rat brain. Neuron. 1992 May;8(5):957–966. doi: 10.1016/0896-6273(92)90210-5. [DOI] [PubMed] [Google Scholar]
  25. Thor S., Ericson J., Brännström T., Edlund T. The homeodomain LIM protein Isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat. Neuron. 1991 Dec;7(6):881–889. doi: 10.1016/0896-6273(91)90334-v. [DOI] [PubMed] [Google Scholar]
  26. Way J. C., Chalfie M. mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans. Cell. 1988 Jul 1;54(1):5–16. doi: 10.1016/0092-8674(88)90174-2. [DOI] [PubMed] [Google Scholar]
  27. Wilkinson D. G., Bailes J. A., Champion J. E., McMahon A. P. A molecular analysis of mouse development from 8 to 10 days post coitum detects changes only in embryonic globin expression. Development. 1987 Apr;99(4):493–500. doi: 10.1242/dev.99.4.493. [DOI] [PubMed] [Google Scholar]
  28. Yancopoulos G. D., Oltz E. M., Rathbun G., Berman J. E., Smith R. K., Lansford R. D., Rothman P., Okada A., Lee G., Morrow M. Isolation of coordinately regulated genes that are expressed in discrete stages of B-cell development. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5759–5763. doi: 10.1073/pnas.87.15.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]

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