The embryonic blood–CSF barrier has molecular elements for specific glucose transport and for the general transport of molecules via transcellular routes
Maryam Parvas, David Bueno
DOI: 10.4236/abb.2010.14041   PDF    HTML     5,520 Downloads   9,810 Views   Citations


In vertebrates, early brain development takes place at the expanded anterior end of the neural tube, which is filled with embryonic cerebrospinal fluid (E-CSF). We have recently identified a transient blood–CSF barrier that forms between embryonic days E3 and E4 in chick embryos and that is responsible for the transport of proteins and control of E-CSF homeostasis, including osmolarity. Here we examined the presence of glucose transporter GLUT-1 as well the presence of caveolae-structural protein Caveolin1 (CAV-1) in the embryonic blood-CSF barrier which may be involved in the transport of glucose and of proteins, water and ions respectively across the neuroectoderm. In this paper we demonstrate the presence of GLUT-1 and CAV-1 in endothelial cells of blood vessels as well as in adjacent neuroectodermal cells, located in the embryonic blood–CSF barrier. In blood vessels, these proteins were detected as early as E4 in chick embryos and E12.7 in rat embryos, i.e. the point at which the embryonic blood–CSF barrier acquires this function. In the neuroectoderm of the embryonic blood-CSF barrier, GLUT-1 was also detected at E4 and E12.7 respectively, and CAV-1 was detected shortly thereafter in both experimental models. These experiments contribute to delineating the extent to which the blood–CSF embryonic barrier controls E-CSF composition and homeostasis during early stages of brain development in avians and mammals. Our results suggest the regulation of glucose transport to the E-CSF by means of GLUT-1 and also suggest a mechanism by which proteins are transported via transcellular routes across the neuroectoderm, thus reinforcing the crucial role of E-CSF in brain development.

Share and Cite:

Parvas, M. and Bueno, D. (2010) The embryonic blood–CSF barrier has molecular elements for specific glucose transport and for the general transport of molecules via transcellular routes. Advances in Bioscience and Biotechnology, 1, 315-321. doi: 10.4236/abb.2010.14041.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Alonso, M.I., Gato, A., Moro, J.A., Martin, P. and Barbosa, E. (1999) Involvement of sulfated proteoglycans in embryonic brain expansion at earliest stages of development in rat embryos. Cells Tissues Organs 165(1), 1-9.
[2] Alonso, M.I., Gato, A., Moro, J.A. and Barbosa, E. (1998) Disruption of proteoglycans in neural tube fluid by D-xyloside alters brain enlargement in chick embryos. The Anatomical Record Part A, 252(4), 499-508.
[3] Desmond, M.E. and Jacobson, A.G. (1977) Embryonic brain enlargement requires cerebrospinal fluid pressure. Developmental Biology, 57(1), 118-198.
[4] Jelinek, R. and Pexieder, T. (1970) Pressure of the CNS in chick embryo. Folia morphologica, 2, 102-110.
[5] Miyan, J.A., Nabiyouni, M. and Zendah, M. (2003) Development of the brain: A vital role for cerebrospinal fluid. Canadian Journal of Physiology and Pharmacology, 81(4), 317-328.
[6] Gato, A. and Desmond, M.E. (2009) Why the embryo still matters: CSF and the neuroepithelium as interdependent regulators of embryonic brain growth, morphogenesis and histiogenesis. Development Biology, 327(2), 263- 272.
[7] Gato, A., Moro, J.A., Alonso, M.I., Bueno, D., De La Mano, A. and Martin. C. (2005) Embryonic cerebrospinal fluid regulates neuroepithelial survival, proliferation, and neurogenesis in chick embryo. The Anatomical Record Part A, 284(1), 475- 484.
[8] Parada, C., Martín, C., Alonso, M.I., Moro, J.A., Bueno, D. and Gato, A. (2005) Embryonic cerebrospinal fluid collaborates with the isthmic organizer to regulate mesencephalic gene expression. Journal of Neuroscience Research, 82(3), 333-345.
[9] Hamburger, V. and Hamilton, H.L. (1951) A series of normal stages in the development of the chick embryo. Journal of Morphology, 88, 49-92.
[10] Parada, C., Gato, A. and Bueno, D. (2005) Mammalian embryonic cerebrospinal fluid proteome has greater apolipoprotein and enzyme pattern complexity than the avian proteome. Journal of Proteome Research, 4(6), 2420- 2428.
[11] Parada, C., Gato, A., Aparicio, M. and Bueno, D. (2006) Proteome analysis of chick embryonic cerebro-spinal fluid. Proteomics, 6(1), 1-34.
[12] Zappaterra, M.D., Lisgo, S.N., Lindsay, S., Gygi, S.P., Walsh, C.A. and Ballif, B.A. (2007) A comparative proteomic analysis of human and rat embryonic cerebrospinal fluid. Journal of Proteomic Research, 6(9), 3537-3548.
[13] Parada, C., Parvas, M. and Bueno, D. (2007) Cerebrospinal fluid proteomes: from neural development to neurodegenerative diseases. Current Proteomics, 4, 89-106.
[14] Parvas, M., Rius, M. and Bueno, D. (2008) Most of the abundant protein fractions of embryonic cerebrospinal fluid are produced out of the brain anlagen. The Open Proteomics Journal, 1, 1-4.
[15] Parvas, M., Parada, C. and Bueno, D. (2008) A blood–CSF barrier function controls embryonic CSF protein composition and homeostasis during early CNS development. Developmental Biology, 321(1), 51-63.
[16] Parvas, M. and Bueno, D. (2010) The embryonic blood-CSF barrier controls E-CSF osmolarity during early CNS development. The Journal of Neuroscience Research, 88(6), 1205-1212.
[17] Rubin, L.L. and Staddon, J.M. (1999) The cell biology of the blood brain barrier. The Annual Review of Neuroscience, 22, 11-28.
[18] Frank, P.G., Woodman, S.E., Park, D.S. and Lisanti, M.P. (2003) Caveolin, caveolae, and endothelial cell function. Arteriosclerosis, Thrombosis, and Vascular Biology, 23, 1161-1168.
[19] Virgintino, D., Robertson, D., Errede, M., Benagiano, V., Taure, U., Roncali, L. and Bertossi, M. (2002) Expression of caveolin-1 in human brain microvessels. Neroscience, 115(1), 145-152.
[20] Dermeitzel, R. and Krause, D. (1991) Molecular anatomy of the blood brain barrier as defined by immunocytochemistry. In: Jeon, K.W. and Friedlander, M. Eds., International review of cytology. Academic Press, New York, 57-109.
[21] Laterra, J. and Goldstein, G.W. (1993) Brain microvessels and microvascular cells in vitro. In: Pardridge, W.M. Eds., The blood-brain barrier, Raven Press, New York, 1-24.
[22] Pardridge, W.M. and Boado, R.J. (1993) Molecular cloning and regulation of gene expression of blood-brain barrier glucose transporter. In: Pardridge, W.M. Eds., The blood-brain barrier, Raven Press, New York, 395-440.
[23] Rahner-Welsch, S., Vogel, J. and Kuschinsky, W. (1995) Regional congruence and divergence of glucose transporters (GLUT1) and capillaries in rat brains. Journal of Cerebral Blood Flow & Metabolism, 15, 681-686.
[24] Bellairs, R. and Osmond, M. (2005) Atlas of Chick Development. Elsevier Academy Press, London.
[25] Dermietzel, R., Krause, D., Kremes, M., Wang, C. and Stevenson, B. (1992) Pattern of glucose transporter (Glut1) expression in embryonic brains is related to maturation of blood-brain barrier tightness. Developmental Dynamics, 193, 152-163.
[26] Harik, S.I., Hall, A.K., Richey, P., Andersson, L., Lundahl, P. and Perry, G. (1993) Ontogeny of the erythroid/ HepG2-type glucose transporter (GLUT-1) in the rat nervous system. Developmental Brain Research, 72, 41- 49.
[27] Bauer, H., Sonnleitner, U., Lametschwandter, A., Steiner, M., Adam, H. and Bauer, H.C. (1995) Ontogenic expression of the erythroid-type glucose transporter (Glut1) in the telencephalon of the mouse: correlation to the tightening of the blood-brain barrier. Developmental Brain Research, 86(1-2), 317-325.
[28] Laemmli, U.K, (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680-685.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.