Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival (original) (raw)

Abstract

We present an initial characterization of the murine Gsh-4 gene which is shown to encode a LIM-type homeodomain. Genes in this category are known to control late developmental cell-type specification events in simpler organisms. Whole mount and serial section in situ hybridizations show transient Gsh-4 expression in ventrolateral regions of the developing neural tube and hindbrain. Mice homozygous for a targeted mutation in Gsh-4 suffer early postnatal death resulting from immature lungs which do not inflate. Prenatal administration of progesterone and glucocorticoid, to extend gestational term and accelerate maturation, resulted in lung inflation at birth. Nevertheless, the hormonally treated mutants generally failed to survive beyond an hour after birth, due to ineffective breathing efforts. It is concluded that Gsh-4 plays a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung.

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  1. Alcorn D., Adamson T. M., Lambert T. F., Maloney J. E., Ritchie B. C., Robinson P. M. Morphological effects of chronic tracheal ligation and drainage in the fetal lamb lung. J Anat. 1977 Jul;123(Pt 3):649–660. [PMC free article] [PubMed] [Google Scholar]
  2. Alcorn D., Adamson T. M., Maloney J. E., Robinson P. M. Morphological effects of chronic bilateral phrenectomy or vagotomy in the fetal lamb lung. J Anat. 1980 Jun;130(Pt 4):683–695. [PMC free article] [PubMed] [Google Scholar]
  3. Barnes J. D., Crosby J. L., Jones C. M., Wright C. V., Hogan B. L. Embryonic expression of Lim-1, the mouse homolog of Xenopus Xlim-1, suggests a role in lateral mesoderm differentiation and neurogenesis. Dev Biol. 1994 Jan;161(1):168–178. doi: 10.1006/dbio.1994.1018. [DOI] [PubMed] [Google Scholar]
  4. Becker K. L., Monaghan K. G., Silva O. L. Immunocytochemical localization of calcitonin in Kulchitsky cells of human lung. Arch Pathol Lab Med. 1980 Apr;104(4):196–198. [PubMed] [Google Scholar]
  5. Boehm T., Foroni L., Kaneko Y., Perutz M. F., Rabbitts T. H. The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4367–4371. doi: 10.1073/pnas.88.10.4367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Candia A. F., Hu J., Crosby J., Lalley P. A., Noden D., Nadeau J. H., Wright C. V. Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development. 1992 Dec;116(4):1123–1136. doi: 10.1242/dev.116.4.1123. [DOI] [PubMed] [Google Scholar]
  7. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Cutz E., Chan W., Track N. S. Bombesin, calcitonin and leu-enkephalin immunoreactivity in endocrine cells of human lung. Experientia. 1981 Jul 15;37(7):765–767. doi: 10.1007/BF01967969. [DOI] [PubMed] [Google Scholar]
  10. Doetschman T. C., Eistetter H., Katz M., Schmidt W., Kemler R. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol. 1985 Jun;87:27–45. [PubMed] [Google Scholar]
  11. 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]
  12. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  13. Ferguson E. L., Sternberg P. W., Horvitz H. R. A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans. Nature. 1987 Mar 19;326(6110):259–267. doi: 10.1038/326259a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Fujii T., Pichel J. G., Taira M., Toyama R., Dawid I. B., Westphal H. Expression patterns of the murine LIM class homeobox gene lim1 in the developing brain and excretory system. Dev Dyn. 1994 Jan;199(1):73–83. doi: 10.1002/aja.1001990108. [DOI] [PubMed] [Google Scholar]
  16. German M. S., Wang J., Chadwick R. B., Rutter W. J. Synergistic activation of the insulin gene by a LIM-homeo domain protein and a basic helix-loop-helix protein: building a functional insulin minienhancer complex. Genes Dev. 1992 Nov;6(11):2165–2176. doi: 10.1101/gad.6.11.2165. [DOI] [PubMed] [Google Scholar]
  17. Graham A., Papalopulu N., Krumlauf R. The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell. 1989 May 5;57(3):367–378. doi: 10.1016/0092-8674(89)90912-4. [DOI] [PubMed] [Google Scholar]
  18. Jansen A. H., Chernick V. Development of respiratory control. Physiol Rev. 1983 Apr;63(2):437–483. doi: 10.1152/physrev.1983.63.2.437. [DOI] [PubMed] [Google Scholar]
  19. Jenkins N. A., Copeland N. G., Taylor B. A., Lee B. K. Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus. J Virol. 1982 Jul;43(1):26–36. doi: 10.1128/jvi.43.1.26-36.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Joyner A. L., Herrup K., Auerbach B. A., Davis C. A., Rossant J. Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox. Science. 1991 Mar 8;251(4998):1239–1243. doi: 10.1126/science.1672471. [DOI] [PubMed] [Google Scholar]
  21. Kalionis B., O'Farrell P. H. A universal target sequence is bound in vitro by diverse homeodomains. Mech Dev. 1993 Sep;43(1):57–70. doi: 10.1016/0925-4773(93)90023-q. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Kern M. J., Witte D. P., Valerius M. T., Aronow B. J., Potter S. S. A novel murine homeobox gene isolated by a tissue specific PCR cloning strategy. Nucleic Acids Res. 1992 Oct 11;20(19):5189–5195. doi: 10.1093/nar/20.19.5189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mansour S. L., Thomas K. R., Capecchi M. R. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature. 1988 Nov 24;336(6197):348–352. doi: 10.1038/336348a0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Michelsen J. W., Schmeichel K. L., Beckerle M. C., Winge D. R. The LIM motif defines a specific zinc-binding protein domain. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4404–4408. doi: 10.1073/pnas.90.10.4404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Rosen B., Beddington R. S. Whole-mount in situ hybridization in the mouse embryo: gene expression in three dimensions. Trends Genet. 1993 May;9(5):162–167. doi: 10.1016/0168-9525(93)90162-b. [DOI] [PubMed] [Google Scholar]
  30. Sadler I., Crawford A. W., Michelsen J. W., Beckerle M. C. Zyxin and cCRP: two interactive LIM domain proteins associated with the cytoskeleton. J Cell Biol. 1992 Dec;119(6):1573–1587. doi: 10.1083/jcb.119.6.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schughart K., Kappen C., Ruddle F. H. Duplication of large genomic regions during the evolution of vertebrate homeobox genes. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7067–7071. doi: 10.1073/pnas.86.18.7067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Singh G., Kaur S., Stock J. L., Jenkins N. A., Gilbert D. J., Copeland N. G., Potter S. S. Identification of 10 murine homeobox genes. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10706–10710. doi: 10.1073/pnas.88.23.10706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stahlman M. T., Jones M., Gray M. E., Kasselberg A. G., Vaughn W. K. Ontogeny of neuroendocrine cells in human fetal lung. III. An electron microscopic immunohistochemical study. Lab Invest. 1987 Jun;56(6):629–641. [PubMed] [Google Scholar]
  34. Taira M., Hayes W. P., Otani H., Dawid I. B. Expression of LIM class homeobox gene Xlim-3 in Xenopus development is limited to neural and neuroendocrine tissues. Dev Biol. 1993 Sep;159(1):245–256. doi: 10.1006/dbio.1993.1237. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. 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]
  37. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wang B. B., Müller-Immergluck M. M., Austin J., Robinson N. T., Chisholm A., Kenyon C. A homeotic gene cluster patterns the anteroposterior body axis of C. elegans. Cell. 1993 Jul 16;74(1):29–42. doi: 10.1016/0092-8674(93)90292-x. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Wigglesworth J. S., Desai R. Effect on lung growth of cervical cord section in the rabbit fetus. Early Hum Dev. 1979 Mar;3(1):51–65. doi: 10.1016/0378-3782(79)90020-3. [DOI] [PubMed] [Google Scholar]
  41. Wigglesworth J. S., Winston R. M., Bartlett K. Influence of the central nervous system on fetal lung development. Experimental study. Arch Dis Child. 1977 Dec;52(12):965–967. doi: 10.1136/adc.52.12.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Xu Y., Baldassare M., Fisher P., Rathbun G., Oltz E. M., Yancopoulos G. D., Jessell T. M., Alt F. W. LH-2: a LIM/homeodomain gene expressed in developing lymphocytes and neural cells. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):227–231. doi: 10.1073/pnas.90.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Youngson C., Nurse C., Yeger H., Cutz E. Oxygen sensing in airway chemoreceptors. Nature. 1993 Sep 9;365(6442):153–155. doi: 10.1038/365153a0. [DOI] [PubMed] [Google Scholar]