Journal of Molecular Neuroscience

, Volume 8, Issue 2, pp 131–143 | Cite as

Myocyte-specific enhancer binding factor 2C expression in fetal mouse brain development

  • Dana Leifer
  • You-Lan Li
  • Kristina Wehr
Original Articles


We have previously found that myocyte-specific enhancer binding factor 2C (MEF2C) is expressed in the brain, where it is found at high levels in the developing cerebral cortex. We have now examined MEF2C expression in fetal mouse brain byin situ hybridization and by immunohistochemistry from E11 to E17, the period when most cortical neurons are born. The distribution of MEF2C mRNA detected byin situ hybridization closely resembles that of MEF2C immunoreactivity. MEF2C is not present in proliferative zones in the brain. It is present at high levels in cells that have migrated to the subplate and cortical plate. MEF2C is also found in the olfactory bulb at high levels and at lower levels in hippocampus, basal forebrain, striatum, cerebellum, and inferior colliculus, and in some nuclei of the hypothalamus, thalamus and brainstem. The pattern of expression suggests that MEF2C is expressed in a subset of postmitotic neurons in the brain and that it may therefore function to promote terminal differentiation of the cells that express it.

Index Entries

Transcription factor brain cerebral cortex postmitotic differentiation RNAin situ hybridization immunohistochemistry mouse embryo 


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  1. Altman J. and Bayer S. A. (1995)Atlas of Prenatal Rat Brain Development. CRC, Boca Raton, FL.Google Scholar
  2. Bartholomä A. and Nave K.-A. (1994) NEX-1: a novel brain-specific helix-loop-helix protein with auto-regulation and sustained expression in mature cortical neurons.Mech. Dev. 48, 217–228.PubMedCrossRefGoogle Scholar
  3. Bayer S. A. and Altman J. (1991)Neocortical Development. Raven, New York.Google Scholar
  4. Breitbart R. E., Liang C.-S., Smoot L. B., Laheru D. A., Mahdavi V., and Nadal-Ginard B. (1993) A fourth human MEF2 transcription factor, hMEF2D, is an early marker of myogenic lineage.Development 118, 1095–1106.PubMedGoogle Scholar
  5. Caviness V. S., Jr. (1982) Neocortical histogenesis in normal and reeler mice: a developmental study based upon [3H]thymidine autoradiography.Dev. Brain Res. 4, 293–302.CrossRefGoogle Scholar
  6. Cserjesi P. and Olson E. N. (1991) Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products.Mol. Cell. Biol. 11, 4854–4862.PubMedGoogle Scholar
  7. Frantz G. D., Bohner A. P., Akers R. M., and McConnell S. K. (1994) Regulation of the POU domain gene SCIP during cerebral cortical development.J. Neurosci. 14, 472–485.PubMedGoogle Scholar
  8. Gardette R., Courtois M., and Bisconte J.-C. (1982) Prenatal development of mouse central nervous structures: time of neuron origin and gradients of neuronal production. A radioautographic study.J. Hirnforsch. 23, 415–431.PubMedGoogle Scholar
  9. Han T.-H. and Prywes R. (1995) Regulatory role of MEF2D in serum induction of the c-jun promoter.Mol. Cell. Biol. 15, 2907–2915.PubMedGoogle Scholar
  10. He X., Treacy M. N., Simmons D. M., Ingraham H. A., Swanson L. A., and Rosenfeld M. G. (1989) Expression of a large family of POU-domain regulatory genes in mammalian brain development.Nature 340, 35–42.PubMedCrossRefGoogle Scholar
  11. Herdegren T., Kiessling M., Bele S., Bravo R., Zimmerman M., and Gass P. (1993) The KROX-20 transcription factor in the rat central and peripheral nervous systems: novel expression pattern of an immediate early gene-encoded protein.Neuroscience 57, 41–52.CrossRefGoogle Scholar
  12. Horlick R. A., Hobson G. M., Patterson J. H., Mitchell M. T., and Benfield P. A. (1990) Brain and muscle creatine kinase genes contain common TA-rich recognition protein-binding regulatory elements.Mol. Cell. Biol. 10, 4826–4836.PubMedGoogle Scholar
  13. Le Moine C. and Young W. S. III (1992)RHS2, a POU domain-containing gene, and its expression in developing adult rat.Proc. Natl. Acad. Sci. USA 89, 3285–3289.PubMedCrossRefGoogle Scholar
  14. Leifer D. (1996) Transcription factors in development of the cerebral cortex.Neuroscientist 2, 7–11.Google Scholar
  15. Leifer D., Golden J., and Kowall N. W. (1994) Myocyte-specific enhancer binding factor 2C expression in human brain development.Neuroscience 63, 1067–1079.PubMedCrossRefGoogle Scholar
  16. Leifer D., Krainc D., Yu Y.-T., McDermott J., Breitbart R. E., Heng J., Neve R. L., Kosofsky B., Nadal-Ginard B., and Lipton S. A. (1993) MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex.Proc. Natl. Acad. Sci. USA 90, 1546–1550.PubMedCrossRefGoogle Scholar
  17. Leifer D. and Wehr K. (1994) Preferential expression of MEF2C in inhibitory interneurons in human cerebral cortex.Soc. Neurosci. Abstracts 20, 1078.Google Scholar
  18. Lyons G. E., Micales B. K., Schwarz J., Martin J. F., and Olson E. N. (1995) Expression ofmef2 genes in the mouse central nervous system suggests a role in neuronal maturation.J. Neurosci. 15, 5727–5738.PubMedGoogle Scholar
  19. Martin J. F., Schwarz J. J., and Olson E. N. (1993) Myocyte enhancer factor (MEF) 2C: a tissue-resticted member of the MEF-2 family of transcription factors.Proc. Natl. Acad. Sci. USA 90, 5282–5286.PubMedCrossRefGoogle Scholar
  20. Martin J. F., Miano J. M., Hustad C. M., Copeland N. G., Jenkins N. A., and Olson E. N. (1994) A MEf2 gene that generates a muscle-specific isoform via alternative mRNA splicing.Mol. Cell. Biol. 14, 1647–1656.PubMedGoogle Scholar
  21. McDermott J. C., Cardoso M. C., Yu Y.-T., Andres V., Leifer D., Krainc D., Lipton S. A., and Nadal-Ginard B. (1993) HMEF2C gene encodes skeletal muscle- and brain-specific transcription factors.Mol. Cell. Biol. 13, 2564–2577.PubMedGoogle Scholar
  22. McGinnis W. and Krumlauf R. (1992) Homeobox genes and axial patterning.Cell 68, 283–302.PubMedCrossRefGoogle Scholar
  23. Rubenstein J. L. R., Martinez S., Shimamura K., and Puelles L. (1994) The embryonic vertebrate forebrain: the prosomeric model.Science 266, 578–580.PubMedCrossRefGoogle Scholar
  24. Schambra U. B., Lauder J. M., and Silver J. (1992)Atlas of the Prenatal Mouse Brain. Academic, San Diego.Google Scholar
  25. Schneider-Mansoury S., Topilko P., Seitanidou T., Levi G., Cohen-Tannoudji M., Pournin S., Babinet C., and Charnay P. (1993) Disruption ofKrox-20 results in alteration of rhombomeres 3 and 5 in developing hindbrain.Cell 75, 1199–1214.CrossRefGoogle Scholar
  26. Sidman R. L. and Rakic P. (1982) Development of the central nervous system, inHistology and Histopathology of the Nervous System (Haymaker W. and Adams, R. D., eds.), C. C. Thomas, Springfield, IL, pp. 3–145.Google Scholar
  27. Simeone A., Acampora D., Gulisano M., Stornaiuolo A., and Boncinelli E. (1992) Nested expression domains of four homeobox genes in developing rostral brain.Nature 358, 687–690.PubMedCrossRefGoogle Scholar
  28. Speliotes E. K., Kowall N. W., Shanti B. F., Kosofsky B., Finklestein S. P., and Leifer D. (1996) MEF2C expression in gerbil brain following global cerebral ischemia.Neuroscience 70, 67–77.PubMedCrossRefGoogle Scholar
  29. Suzuki E., Guo K., Kolman M., Yu Y.-T., and Walsh K. (1995) Serum induction of MEF2/RSRF expression in vascular myocytes is mediated at the level of translation.Mol. Cell. Biol. 15, 3415–3423.PubMedGoogle Scholar
  30. Wilkinson D. G., Bhatt S., Cook M., Boncinelli E., and Krumlauf R. (1989) Segmental expression of Hox-2 homeobox-containing genes in the developing mouse hindbrain.Nature 341, 405–409.PubMedCrossRefGoogle Scholar
  31. Yu Y.-T., Breitbart R. E., Smoot L. B., Lee Y., Mahdavi V., and Nadal-Ginard B. (1992) Human myocyte-specific factor 2 (MEF2) comprises a group of tissue restricted MADS box transcription factors.Genes Dev. 6, 1783–1798.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 1997

Authors and Affiliations

  • Dana Leifer
    • 1
  • You-Lan Li
    • 1
  • Kristina Wehr
    • 1
  1. 1.Department of NeurologyYale University School of Medicine, LC17New Haven

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