Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1993 Jan;13(1):105–113. doi: 10.1128/mcb.13.1.105

A rat gene with sequence homology to the Drosophila gene hairy is rapidly induced by growth factors known to influence neuronal differentiation.

J N Feder 1, L Y Jan 1, Y N Jan 1
PMCID: PMC358890  PMID: 8417318

Abstract

Several genes encoding transcription factors with a helix-loop-helix (HLH) motif are involved in the early process of neural development in Drosophila spp. We report the isolation from the rat a homolog of one of these genes, called hairy. The rat-hairy-like (RHL) gene is expressed early during embryogenesis. In contrast to the restricted expression of hairy mRNA in Drosophila spp., however, the mRNA encoded by RHL is detectable in all tissues examined. Stimulation of PC12 pheochromocytoma cells by nerve growth factor, basis fibroblast growth factor, or epidermal growth factor or of Rat-1 fibroblasts by epidermal growth factor causes a rapid and transient induction of the RHL gene. Thus, RHL acts as an immediate-early gene that can potentially transduce growth factor signals during the development of the mammalian embryo.

Full text

PDF
105

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. J. The neural crest cell lineage problem: neuropoiesis? Neuron. 1989 Jul;3(1):1–12. doi: 10.1016/0896-6273(89)90110-4. [DOI] [PubMed] [Google Scholar]
  2. Artavanis-Tsakonas S. The molecular biology of the Notch locus and the fine tuning of differentiation in Drosophila. Trends Genet. 1988 Apr;4(4):95–100. doi: 10.1016/0168-9525(88)90096-0. [DOI] [PubMed] [Google Scholar]
  3. Baker N. E. Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos. EMBO J. 1987 Jun;6(6):1765–1773. doi: 10.1002/j.1460-2075.1987.tb02429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bartel D. P., Sheng M., Lau L. F., Greenberg M. E. Growth factors and membrane depolarization activate distinct programs of early response gene expression: dissociation of fos and jun induction. Genes Dev. 1989 Mar;3(3):304–313. doi: 10.1101/gad.3.3.304. [DOI] [PubMed] [Google Scholar]
  5. Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. doi: 10.1016/0092-8674(90)90214-y. [DOI] [PubMed] [Google Scholar]
  6. Boonstra J., Moolenaar W. H., Harrison P. H., Moed P., van der Saag P. T., de Laat S. W. Ionic responses and growth stimulation induced by nerve growth factor and epidermal growth factor in rat pheochromocytoma (PC12) cells. J Cell Biol. 1983 Jul;97(1):92–98. doi: 10.1083/jcb.97.1.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Botas J., Moscoso del Prado J., García-Bellido A. Gene-dose titration analysis in the search of trans-regulatory genes in Drosophila. EMBO J. 1982;1(3):307–310. doi: 10.1002/j.1460-2075.1982.tb01165.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cabrera C. V., Alonso M. C. Transcriptional activation by heterodimers of the achaete-scute and daughterless gene products of Drosophila. EMBO J. 1991 Oct;10(10):2965–2973. doi: 10.1002/j.1460-2075.1991.tb07847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cabrera C. V., Martinez-Arias A., Bate M. The expression of three members of the achaete-scute gene complex correlates with neuroblast segregation in Drosophila. Cell. 1987 Jul 31;50(3):425–433. doi: 10.1016/0092-8674(87)90496-x. [DOI] [PubMed] [Google Scholar]
  10. Campos-Ortega J. A., Jan Y. N. Genetic and molecular bases of neurogenesis in Drosophila melanogaster. Annu Rev Neurosci. 1991;14:399–420. doi: 10.1146/annurev.ne.14.030191.002151. [DOI] [PubMed] [Google Scholar]
  11. Campuzano S., Modolell J. Patterning of the Drosophila nervous system: the achaete-scute gene complex. Trends Genet. 1992 Jun;8(6):202–208. doi: 10.1016/0168-9525(92)90234-u. [DOI] [PubMed] [Google Scholar]
  12. Caudy M., Vässin H., Brand M., Tuma R., Jan L. Y., Jan Y. N. daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex. Cell. 1988 Dec 23;55(6):1061–1067. doi: 10.1016/0092-8674(88)90250-4. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Christy B. A., Sanders L. K., Lau L. F., Copeland N. G., Jenkins N. A., Nathans D. An Id-related helix-loop-helix protein encoded by a growth factor-inducible gene. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1815–1819. doi: 10.1073/pnas.88.5.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cubas P., de Celis J. F., Campuzano S., Modolell J. Proneural clusters of achaete-scute expression and the generation of sensory organs in the Drosophila imaginal wing disc. Genes Dev. 1991 Jun;5(6):996–1008. doi: 10.1101/gad.5.6.996. [DOI] [PubMed] [Google Scholar]
  16. Danielson P. E., Forss-Petter S., Brow M. A., Calavetta L., Douglass J., Milner R. J., Sutcliffe J. G. p1B15: a cDNA clone of the rat mRNA encoding cyclophilin. DNA. 1988 May;7(4):261–267. doi: 10.1089/dna.1988.7.261. [DOI] [PubMed] [Google Scholar]
  17. Davis R. L., Cheng P. F., Lassar A. B., Weintraub H. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell. 1990 Mar 9;60(5):733–746. doi: 10.1016/0092-8674(90)90088-v. [DOI] [PubMed] [Google Scholar]
  18. Doupe A. J., Landis S. C., Patterson P. H. Environmental influences in the development of neural crest derivatives: glucocorticoids, growth factors, and chromaffin cell plasticity. J Neurosci. 1985 Aug;5(8):2119–2142. doi: 10.1523/JNEUROSCI.05-08-02119.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ellis H. M., Spann D. R., Posakony J. W. extramacrochaetae, a negative regulator of sensory organ development in Drosophila, defines a new class of helix-loop-helix proteins. Cell. 1990 Apr 6;61(1):27–38. doi: 10.1016/0092-8674(90)90212-w. [DOI] [PubMed] [Google Scholar]
  20. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  21. Feder J. N., Guidos C. J., Kusler B., Carswell C., Lewis D., Schimke R. T. A cell cycle analysis of growth-related genes expressed during T lymphocyte maturation. J Cell Biol. 1990 Dec;111(6 Pt 1):2693–2701. doi: 10.1083/jcb.111.6.2693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Freytag S. O., Geddes T. J. Reciprocal regulation of adipogenesis by Myc and C/EBP alpha. Science. 1992 Apr 17;256(5055):379–382. doi: 10.1126/science.256.5055.379. [DOI] [PubMed] [Google Scholar]
  23. Ghysen A., Dambly-Chaudiere C. Genesis of the Drosophila peripheral nervous system. Trends Genet. 1989 Aug;5(8):251–255. doi: 10.1016/0168-9525(89)90097-8. [DOI] [PubMed] [Google Scholar]
  24. Goelet P., Castellucci V. F., Schacher S., Kandel E. R. The long and the short of long-term memory--a molecular framework. 1986 Jul 31-Aug 6Nature. 322(6078):419–422. doi: 10.1038/322419a0. [DOI] [PubMed] [Google Scholar]
  25. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  26. Greene L. A., Tischler A. S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424–2428. doi: 10.1073/pnas.73.7.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ito E., Sonnenberg J. L., Narayanan R. Nerve growth factor-induced differentiation in PC-12 cells is blocked by fos oncogene. Oncogene. 1989 Oct;4(10):1193–1199. [PubMed] [Google Scholar]
  28. Ito E., Sweterlitsch L. A., Tran P. B., Rauscher F. J., 3rd, Narayanan R. Inhibition of PC-12 cell differentiation by the immediate early gene fra-1. Oncogene. 1990 Dec;5(12):1755–1760. [PubMed] [Google Scholar]
  29. Jan Y. N., Jan L. Y. Genes required for specifying cell fates in Drosophila embryonic sensory nervous system. Trends Neurosci. 1990 Dec;13(12):493–498. doi: 10.1016/0166-2236(90)90083-m. [DOI] [PubMed] [Google Scholar]
  30. Jessell T. M., Melton D. A. Diffusible factors in vertebrate embryonic induction. Cell. 1992 Jan 24;68(2):257–270. doi: 10.1016/0092-8674(92)90469-s. [DOI] [PubMed] [Google Scholar]
  31. Johnson J. E., Birren S. J., Anderson D. J. Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors. Nature. 1990 Aug 30;346(6287):858–861. doi: 10.1038/346858a0. [DOI] [PubMed] [Google Scholar]
  32. Johnson J. E., Zimmerman K., Saito T., Anderson D. J. Induction and repression of mammalian achaete-scute homologue (MASH) gene expression during neuronal differentiation of P19 embryonal carcinoma cells. Development. 1992 Jan;114(1):75–87. doi: 10.1242/dev.114.1.75. [DOI] [PubMed] [Google Scholar]
  33. Klämbt C., Knust E., Tietze K., Campos-Ortega J. A. Closely related transcripts encoded by the neurogenic gene complex enhancer of split of Drosophila melanogaster. EMBO J. 1989 Jan;8(1):203–210. doi: 10.1002/j.1460-2075.1989.tb03365.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Knust E., Dietrich U., Tepass U., Bremer K. A., Weigel D., Vässin H., Campos-Ortega J. A. EGF homologous sequences encoded in the genome of Drosophila melanogaster, and their relation to neurogenic genes. EMBO J. 1987 Mar;6(3):761–766. doi: 10.1002/j.1460-2075.1987.tb04818.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lo L. C., Johnson J. E., Wuenschell C. W., Saito T., Anderson D. J. Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells. Genes Dev. 1991 Sep;5(9):1524–1537. doi: 10.1101/gad.5.9.1524. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Michelson A. M., Abmayr S. M., Bate M., Arias A. M., Maniatis T. Expression of a MyoD family member prefigures muscle pattern in Drosophila embryos. Genes Dev. 1990 Dec;4(12A):2086–2097. doi: 10.1101/gad.4.12a.2086. [DOI] [PubMed] [Google Scholar]
  38. Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
  39. Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. doi: 10.1016/0092-8674(89)90434-0. [DOI] [PubMed] [Google Scholar]
  40. Nepveu A., Marcu K. B. Intragenic pausing and anti-sense transcription within the murine c-myc locus. EMBO J. 1986 Nov;5(11):2859–2865. doi: 10.1002/j.1460-2075.1986.tb04580.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Padgett R. W., St Johnston R. D., Gelbart W. M. A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-beta family. Nature. 1987 Jan 1;325(6099):81–84. doi: 10.1038/325081a0. [DOI] [PubMed] [Google Scholar]
  42. Romani S., Campuzano S., Macagno E. R., Modolell J. Expression of achaete and scute genes in Drosophila imaginal discs and their function in sensory organ development. Genes Dev. 1989 Jul;3(7):997–1007. doi: 10.1101/gad.3.7.997. [DOI] [PubMed] [Google Scholar]
  43. Romani S., Campuzano S., Modolell J. The achaete-scute complex is expressed in neurogenic regions of Drosophila embryos. EMBO J. 1987 Jul;6(7):2085–2092. doi: 10.1002/j.1460-2075.1987.tb02474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Rushlow C. A., Hogan A., Pinchin S. M., Howe K. M., Lardelli M., Ish-Horowicz D. The Drosophila hairy protein acts in both segmentation and bristle patterning and shows homology to N-myc. EMBO J. 1989 Oct;8(10):3095–3103. doi: 10.1002/j.1460-2075.1989.tb08461.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rydel R. E., Greene L. A. Acidic and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells. J Neurosci. 1987 Nov;7(11):3639–3653. doi: 10.1523/JNEUROSCI.07-11-03639.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sheng M., Greenberg M. E. The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron. 1990 Apr;4(4):477–485. doi: 10.1016/0896-6273(90)90106-p. [DOI] [PubMed] [Google Scholar]
  47. Skeath J. B., Carroll S. B. Regulation of achaete-scute gene expression and sensory organ pattern formation in the Drosophila wing. Genes Dev. 1991 Jun;5(6):984–995. doi: 10.1101/gad.5.6.984. [DOI] [PubMed] [Google Scholar]
  48. Spencer F. A., Hoffmann F. M., Gelbart W. M. Decapentaplegic: a gene complex affecting morphogenesis in Drosophila melanogaster. Cell. 1982 Mar;28(3):451–461. doi: 10.1016/0092-8674(82)90199-4. [DOI] [PubMed] [Google Scholar]
  49. Stein R., Orit S., Anderson D. J. The induction of a neural-specific gene, SCG10, by nerve growth factor in PC12 cells is transcriptional, protein synthesis dependent, and glucocorticoid inhibitable. Dev Biol. 1988 Jun;127(2):316–325. doi: 10.1016/0012-1606(88)90318-1. [DOI] [PubMed] [Google Scholar]
  50. Togari A., Dickens G., Kuzuya H., Guroff G. The effect of fibroblast growth factor on PC12 cells. J Neurosci. 1985 Feb;5(2):307–316. doi: 10.1523/JNEUROSCI.05-02-00307.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Unsicker K., Krisch B., Otten U., Thoenen H. Nerve growth factor-induced fiber outgrowth from isolated rat adrenal chromaffin cells: impairment by glucocorticoids. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3498–3502. doi: 10.1073/pnas.75.7.3498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Vaessin H., Caudy M., Bier E., Jan L. Y., Jan Y. N. Role of helix-loop-helix proteins in Drosophila neurogenesis. Cold Spring Harb Symp Quant Biol. 1990;55:239–245. doi: 10.1101/sqb.1990.055.01.026. [DOI] [PubMed] [Google Scholar]
  53. Van Doren M., Ellis H. M., Posakony J. W. The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaete-scute protein complexes. Development. 1991 Sep;113(1):245–255. doi: 10.1242/dev.113.1.245. [DOI] [PubMed] [Google Scholar]
  54. Villares R., Cabrera C. V. The achaete-scute gene complex of D. melanogaster: conserved domains in a subset of genes required for neurogenesis and their homology to myc. Cell. 1987 Jul 31;50(3):415–424. doi: 10.1016/0092-8674(87)90495-8. [DOI] [PubMed] [Google Scholar]
  55. van den Heuvel M., Nusse R., Johnston P., Lawrence P. A. Distribution of the wingless gene product in Drosophila embryos: a protein involved in cell-cell communication. Cell. 1989 Nov 17;59(4):739–749. doi: 10.1016/0092-8674(89)90020-2. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES