Reelin, Liver, and Lymphatics

  • Brigitte Samama
  • Nelly Boehm

Reelin, as an extracellular glycoprotein involved in neuronal migration and cerebral cortex layering pattern, has received much attention since the discovery of the gene responsible for the disturbed central nervous system development in the reeler mouse, because of its fundamental functions in cerebral development, its modulatory effects on synaptic plasticity in adult rodents, and its potential involvement in psychiatric disorders (for recent reviews and references see: Jossin, 2004; D’Arcangelo, 2005; Fatemi, 2005; Forster et al., 2006; Herz and Chen, 2006). Our knowledge about effects that reelin may have on peripheral organs, however, remains very scarce. Reelin mRNA and protein have been detected during development and adulthood in several peripheral organs. In the present chapter, we will focus on the presence of reelin in liver and lymphatics and discuss some hypotheses about the functional significance of this presence.


Stellate Cell Hepatic Stellate Cell Lipoprotein Receptor Peripheral Organ Lymphatic Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Botella-Lopez, A., Burgaya, F., Gavin, R., Garcia-Ayllon, M.S., Gomez-Tortosa, E., Pena-Casanova, J., Urena, J.M., Del Rio, J.A., Blesa, R., Soriano, E., and Saez-Valero, J. (2006). Reelin expression and glycosylation patterns are altered in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 103: 5573-5578.CrossRefPubMedGoogle Scholar
  2. Buniatian, G., Hamprecht, B., and Gebhardt, R. (1996). Glial fibrillary acidic protein as a marker of perisinusoidal stellate cells that can distinguish between the normal and myofibroblast-like phenotypes. Biol. Cell. 87: 65-73.CrossRefPubMedGoogle Scholar
  3. Cariboni, A., Rakic, S., Liapi, A., Maggi, R., Goffinet, A., and Parnavelas, J. G. (2005). Reelin provides an inhibitory signal in the migration of gonadotropin-releasing hormone neurons. Development 132: 4709-4718.CrossRefPubMedGoogle Scholar
  4. Cassiman, D., Barlow, A., Vander Borght, S., Libbrecht, L., and Pachnis, V. (2006). Hepatic stel-late cells do not derive from the neutral crest. J. Hepatol. 44: 1098-1104.CrossRefPubMedGoogle Scholar
  5. Curran, T., and D’Arcangelo, G. (1998). Role of reelin in the control of brain development. Brain Res. Brain Res. Rev. 26: 285-294.CrossRefPubMedGoogle Scholar
  6. D’Arcangelo, G. (2005). The reeler mouse: anatomy of a mutant. Int. Rev. Neurobiol. 71: 383-417.CrossRefPubMedGoogle Scholar
  7. De Bergeyck, V., Naerhuyzen, B., Goffinet, A. M., and Lambert de Rouvroit, C. (1998). A panel of monoclonal antibodies against reelin, the extracellular matrix protein defective in reeler mutant mice. J. Neurosci. Methods 82: 17-24.CrossRefPubMedGoogle Scholar
  8. DeSilva, U., D’Arcangelo, G., Braden, V. V., Chen, J., Miao, G. G., Curran, T., and Green, E. D. (1997). The human reelin gene: isolation, sequencing and mapping on chromosome 7. Genome Res. 7: 157-164.CrossRefPubMedGoogle Scholar
  9. Dulabon, L., Olson, E. C., Taglienti, M. G., Eisenhuth, S., McGrath, B, Walsh, C. A., Kreidberg, J. A., and Anton, E. S. (2000). Reelin binds alpha3beta1 integrin and inhibits neuronal migration. Neuron 27: 33-44.CrossRefPubMedGoogle Scholar
  10. Enzan, H., Himeno, H., Hiroi, M., Kiyoku, H., Saibara, T., and Onishi, S. (1997). Development of hepatic sinusoidal structure with special reference to the Ito cells. Microsc. Res. Tech. 39: 336-349.CrossRefPubMedGoogle Scholar
  11. Fatemi, S. H. (2005). Reelin glycoprotein in autism and schizophrenia. Int. Rev. Neurobiol. 71: 179-187.CrossRefPubMedGoogle Scholar
  12. Forster, E., Jossin, Y., Zhao, S., Chai, X., Frotscher, M., and Goffinet A. M. (2006). Recent progress in understanding the role of reelin in radial neuronal migration, with specific empha-sis on the dentate gyrus. Eur. J. Neurosci. 23: 901-909.CrossRefPubMedGoogle Scholar
  13. Geersts, A. (2004). On the origin of stellate cells: mesodermal, endodermal or neuro-ectodermal? J. Hepatol. 40: 331-334.CrossRefGoogle Scholar
  14. Gressner, A. M., and Weiskirchen, R. (2006). Modern pathogenetic concepts of liver fibrosis sug-gest stellate cells and TGF-beta as major players and therapeutic targets. J. Cell. Mol. Med. 10: 76-99.CrossRefPubMedGoogle Scholar
  15. Herz, J., and Chen, Y. (2006). Reelin, lipoprotein receptors and synaptic plasticity. Nature Rev. Neurosci. 7: 850-859.CrossRefGoogle Scholar
  16. Hirotsune, S., Takahara, T., Sasaki, N., Hirose, K., Yoshiki, A., Ohashi, T., Kusakabe, M., Murakami, Y., Muramatsu, M., Watanabe, S., Nakao, K., Katsuki, M., and Hayashizaki, Y. (1995). The reeler gene encodes a protein with an EGF-like motif expressed by pioneer neu-rons. Nature Genet. 10: 77-83.CrossRefPubMedGoogle Scholar
  17. Hong, S. E., Shugart, Y. Y., Huang, D. T., Shahwan, S. A., Grant, P. E., Hourihane, J. O., Martin, N. D., and Walsh, C. A. (2000). Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nature Genet. 26: 93-96.CrossRefPubMedGoogle Scholar
  18. Hourihane, J. O., Bennett, C. P., Chaudhuri, R., Robb, S. A., and Martin, N. D. (1993). A sibship with a neuronal migration defect, cerebellar hypoplasia and congenital lymphedema. Neuropediatrics 24: 43-46.CrossRefPubMedGoogle Scholar
  19. Howell, B. W., Gertler, F. B., and Cooper, J. A. (1997). Mouse disabled (mDab1): a Src binding protein implicated in neural development. EMBO J. 16: 121-132.CrossRefPubMedGoogle Scholar
  20. Ignatova, N., Sindic, C. J., and Goffinet, A. M. (2004). Characterization of the various forms of the reelin protein in the cerebrospinal fluid of normal subjects and in neurological diseases. Neurobiol. Dis. 15: 326-330.CrossRefPubMedGoogle Scholar
  21. Ikeda, Y., and Terashima, T. (1997). Expression of reelin, the gene responsible for the reeler muta-tion in embryonic development and adulthood in the mouse. Dev. Dyn. 210: 157-172.CrossRefPubMedGoogle Scholar
  22. Jossin, Y. (2004). Neuronal migration and the role of reelin during early development of the cere-bral cortex. Mol. Neurobiol. 30: 225-251.CrossRefPubMedGoogle Scholar
  23. Jossin, Y., Bar, I., Ignatova, N., Tissir, F., Lambert de Rouvroit, C., and Goffinet, A. M. (2003). The reelin signalling pathway: some recent developments. Cereb. Cortex 13: 627-633.CrossRefPubMedGoogle Scholar
  24. Kim, D. H., Iijima, H., Goto, K., Ishii, H., Kim, H. J., Suzuki, H., Kondo, H., Saeki, S., and Yamamoto, T. (1996). Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain. J. Biol. Chem. 271: 8373-8380.CrossRefPubMedGoogle Scholar
  25. Kobold, D., Grundmann, A., Piscaglia, F., Eisenbach, C., Neubauer, K., Steffgen, J., Ramadori, G., and Knittel, T. (2002). Expression of reelin in hepatic stellate cells and during hepatic tissue repair: a novel marker for the differentiation of HSC from other liver myofibroblasts. J. Hepatol. 36: 607-613.CrossRefPubMedGoogle Scholar
  26. Kubasak, M. D., Brooks, R., Chen, S., Villeda, S. A., and Phelps, P. E. (2004). Developmental distribution of reelin-positive cells and their secreted product in the rodent spinal cord. J. Comp. Neurol. 468: 165-178.CrossRefPubMedGoogle Scholar
  27. Le Douarin, N. M.(1975). An experimental analysis of liver development. Med. Biol. 53: 427-455.PubMedGoogle Scholar
  28. Lugli, G., Krueger, J. M., Davis, J. M., Persico, A. M., and Smalheiser, N. R. (2003). Methodological factors influencing measurement and processing of plasma reelin in humans. BMC Biochem. 4:9.CrossRefPubMedGoogle Scholar
  29. Maurin, J. C., Couble, M. L., Didier-Bazes, M., Brisson, C., Magloire, H., and Bleicher, F. (2004). Expression and localization of reelin in human odontoblasts. Matrix Biol. 23: 277-285.CrossRefPubMedGoogle Scholar
  30. May, P., Herz, J., and Bock, H. H. (2005). Molecular mechanisms of lipoprotein receptor signal-ling. Cell. Mol. Life Sci. 62: 2325-2338.CrossRefPubMedGoogle Scholar
  31. Meyer, G., Lambert de Rouvroit, C., Goffinet, A. M., and Wahle, P. (2003). Disabled-1 mRNA and protein expression in developing human cortex. Eur. J. Neurosci. 17: 517-525.CrossRefPubMedGoogle Scholar
  32. Perez-Garcia, C. G., Tissir, F., Goffinet, A. M., and Meyer, G. (2004). Reelin receptors in develop-ing laminated brain structures of mouse and human. Eur. J. Neurosci. 20: 2827-2832.CrossRefPubMedGoogle Scholar
  33. Re, R. N., and Cook, J. L. (2006). The intracrine hypothesis: an update. Regul. Pept. 133: 1-9.CrossRefPubMedGoogle Scholar
  34. Roberts, R. C., Xu, L., Roche, J. K., and Kirkpatrick, B. (2005). Ultrastructural localization of reelin in the cortex in post-mortem human brain. J. Comp. Neurol. 482: 294-308.CrossRefPubMedGoogle Scholar
  35. Samama, B., and Boehm, N. (2005). Reelin immunoreactivity in lymphatics and liver during development and adult life. Anat. Rec. A 285: 595-599.Google Scholar
  36. Senoo, H. (2004). Structure and function of hepatic stellate cells. Med. Electron Microsc. 37: 3-15.CrossRefPubMedGoogle Scholar
  37. Smalheiser, N. R., Costa, E., Guidotti, A., Impagnatiello, F., Auta, J., Lacor, P., Kriho, V., and Pappas, G. D. (2000). Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells. Proc. Natl. Acad. Sci. USA 97: 1281-1286.CrossRefPubMedGoogle Scholar
  38. Soriano, E., and Del Rio, J. A. (2005). The cells of Cajal-Retzius: still a mystery one century after. Neuron 46: 389-394.CrossRefPubMedGoogle Scholar
  39. Stolt, P. C., and Bock, H. H. (2006). Modulation of lipoprotein receptor functions by intracellular adaptor proteins. Cell Signal. 18: 1560-1571.CrossRefPubMedGoogle Scholar
  40. Takahashi, S., Sakai, J., Fujino, T., Hattori, H., Zenimaru, Y., Suzuki, J., Miyamori, I., and Yamamoto, T. T. (2004). The very low-density lipoprotein (VLDL) receptor: characterization and functions as a peripheral lipoprotein receptor. J. Atheroscler. Thromb. 11: 200-208.PubMedGoogle Scholar
  41. Tissir, F., and Goffinet, A. M. (2003). Reelin and brain development. Nature Rev. Neurosci. 4: 496-505.CrossRefGoogle Scholar
  42. Wilting, J., and Becker, J. (2006). Two endothelial cell lines derived from the somite. Anat. Embryol. (Berl.) 211 (Suppl. 7): 57-63.Google Scholar
  43. Yip, J. W., Yip, Y. P., Nakajima, K., and Capriotti, C. (2000). Reelin controls position of auto-nomic neurons in the spinal cord. Proc. Natl. Acad. Sci. USA 97: 8612-8616.CrossRefPubMedGoogle Scholar
  44. Yip, Y. P., Capriotti, C., and Yip, J. W. (2003). Migratory pathway of sympathetic preganglionic neurons in normal and reeler mutant mice. J. Comp. Neurol. 460: 94-105.CrossRefPubMedGoogle Scholar
  45. Yip, Y. P., Capriotti, C., Magdaleno, S., Benhayon, D., Curran, T., Nakajima, K., and Yip, J. W. (2004). Components of the reelin signalling pathway are expressed in the spinal cord. J. Comp. Neurol. 470: 210-219.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Brigitte Samama
    • 1
  • Nelly Boehm
    • 1
  1. 1.Institut d’Histologie, Faculté de MédecineUniversité Louis PasteurStrasbourg CedexFrance

Personalised recommendations