Abstract
1. Although recent advances have provided insight into the transcriptional control of oligodendrocyte (OG) development, little information exists on the role of clustered Hox genes in this process. The aim of this study was to examine the expression profile of Hoxb4 in the oligodendroglial lineage.
2. Immunocytochemical analysis of primary mixed glial cultures demonstrated that Hoxb4 was expressed throughout OG development, being coexpressed with oligodendroglial markers, A2B5, O4 (97%), GalC (91%), and MBP (93%).
3. Immunohistochemical analysis of transverse spinal cord sections demonstrated diffuse expression of Hoxb4 throughout the spinal cord at E12.5 (C16/T19), after which expression was confined primarily to the presumptive gray matter.
4. At E14.25 (C19+/T21), Olig2+ cells had begun to migrate out from the ventral ventricular zone into the presumptive gray matter. These results suggest that Olig2+ cells could coexpress Hoxb4 since it is expressed throughout this region.
5. The expression of Hoxb4 by cells of the OG lineage indicates that it could play a role in OG maturation.
Keywords: oligodendrocyte development, Hoxb4, Olig2, primary glial cultures, spinal cord
REFERENCES
- Abney, E. R., Williams, B. P., and Raff, M. C. (1983). Tracing the development of oligodendrocytes from precursor cells using monoclonal antibodies, fluorescence-activated cell sorting, and cell culture. Dev. Biol.100:166-171. [DOI] [PubMed] [Google Scholar]
- Armstrong, R. C., Kim, J. G., and Hudson, L. D. (1995). Expression of myelin transcription factor I (MyTI), a “zinc-finger” DNA-binding protein, in developing oligodendrocytes. Glia14:303-321. [DOI] [PubMed] [Google Scholar]
- Asou, H., Hamada, K., Miyazaki, T., Sakota, T., Hayashi, K., Takeda, Y., Marret, S., Delpech, B., Itoh, K., and Uyemura, K. (1995). CNS myelinogenesis in vitro: Time course and pattern of rat oligodendrocyte development. J. Neurosci. Res.40:519-534. [DOI] [PubMed] [Google Scholar]
- Bansal, R., Warrington, A. E., Gard, A. L., Ranscht, B., and Pfeiffer, S. E. (1989). Multiple and novel specificities of monoclonal antibodies O1, O4, and R-mAb used in the analysis of oligodendrocyte development. J. Neurosci. Res.24:548-557. [DOI] [PubMed] [Google Scholar]
- Barres, B. A., Lazar, M. A., and Raff, M. C. (1994). A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development120:1097-1108. [DOI] [PubMed] [Google Scholar]
- Butler, H., and Juurlink, B. H. J. (1987). An Atlas for Staging Mammalian and Chick Embryos, CRC Press, Boca Raton, FL, pp. 89-100. [Google Scholar]
- Doucette, R., and Devon, R. (1994). Media that support the growth and differentiation of oligodendrocytes do not induce olfactory ensheathing cells to express a myelinating phenotype. Glia10:296-310. [DOI] [PubMed] [Google Scholar]
- Duchala, C. S., Asotra, K., and Macklin, W. B. (1995). Expression of cell surface markers and myelin proteins in cultured oligodendrocytes from neonatal brain of rat and mouse: A comparative study. Dev. Neurosci.17:70-80. [DOI] [PubMed] [Google Scholar]
- Favier, B., and Dollé, P. (1997). Developmental functions of mammalian Hox genes. Mol. Human Reprod.3:115-131. [DOI] [PubMed] [Google Scholar]
- Fok-Seang, J., and Miller, R. H. (1994). Distribution and differentiation of A2B5+ glial precursors in the developing rat spinal cord. J. Neurosci. Res.37:219-235. [DOI] [PubMed] [Google Scholar]
- Gard, A. L., and Pfeiffer, S. E. (1990). Two proliferative stages of the oligodendrocyte lineage (A2B5+ O4- and O4+ GalC-) under different mitogenic control. Neuron5:615-625. [DOI] [PubMed] [Google Scholar]
- Gaunt, S. J., Krumlauf, R., and Duboule, D. (1989). Mouse homeo-genes within a subfamily, Hox-1.4,-2.6 and-5.1, display similar anteroposterior domains of expression in the embryo, but show stage-and tissue-dependent differences in their regulation. Development107:131-141. [DOI] [PubMed] [Google Scholar]
- Gould, A., Itasaki, N., and Krumlauf, R. (1998). Initiation of rhombomeric Hoxb4 expression requires induction by somites and a retinoid pathway. Neuron21:39-51. [DOI] [PubMed] [Google Scholar]
- Graham, A., Maden, M., and Krumlauf, R. (1991). The murine Hox-2 genes display dynamic dorsoventral patterns of expression during central nervous system development. Development112:255-264. [DOI] [PubMed] [Google Scholar]
- Graham, A., Papalopulu, N., and Krumlauf, R. (1989). The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell57:367-378. [DOI] [PubMed] [Google Scholar]
- Graham, A., Papalopulu, N., Lorimer, J., McVey, J. H., Tuddenham, E. G. D., and Krumlauf, R. (1988). Characterization of a murine homeobox gene, Hox-2.6, related to the Drosophila Deformed gene. Genes Develop.2:1424-1438. [DOI] [PubMed] [Google Scholar]
- Han, K., Levine, M. S., and Manley, J. L. (1989). Synergistic activation and repression of transcription by Drosophila homeobox proteins. Cell56:573-583. [DOI] [PubMed] [Google Scholar]
- Hao, Z., Yeung, J., Wolf, L., Doucette, R., and Nazarali, A. (1999). Differential expression of Hoxa-2 protein along the dorsal-ventral axis of the developing and adult mouse spinal cord. Dev. Dyn.216:201-217. [DOI] [PubMed] [Google Scholar]
- Hoey, T., and Levine, M. (1988). Divergent homeo box proteins recognize similar DNA sequences in Drosophila. Nature332:858-861. [DOI] [PubMed] [Google Scholar]
- Ibarrola, N., Mayer-Pröschel, M., Rodriguez-Peña, A., and Noble, M. (1996). Evidence for the existence of at least two timing mechanisms that contribute to oligodendrocyte generation In vitro. Dev. Biol.180:1-21. [DOI] [PubMed] [Google Scholar]
- Kissinger, C. R., Liu, B., Martin-Blanco, E., Kornberg, T. B., and Pabo, C. O. (1990). Crystal structure of an engrailed homeodomain-DNA complex at 2.8 å resolution: A framework for understanding homeodomain-DNA interactions. Cell63:579-590. [DOI] [PubMed] [Google Scholar]
- Lu, Q. R., Sun, T., Zhu, Z., Ma, N., Garcia, M., Stiles, C. D., and Rowitch, D. H. (2002). Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell109:75-86. [DOI] [PubMed] [Google Scholar]
- Lu, Q. R., Yuk, D., Alberta, J. A., Zhu, Z., Pawlitzky, I., Chan, J., McMahon, A. P., Stiles, C. D., and Rowitch, D. H. (2000). Sonic hedgehog-regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron25:317-329. [DOI] [PubMed] [Google Scholar]
- McGinnis, W., Garber, R. L., Wirz, J., Kuroiwa, A., and Gehring, W. J. (1984a). A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell37:403-408. [DOI] [PubMed] [Google Scholar]
- McGinnis, W., Hart, C. P., Gehring, W. J., and Ruddle, F. H. (1984b). Molecular cloning and chromosome mapping of a mouse DNA sequence homologous to homeotic genes of Drosophila. Cell38:675-680. [DOI] [PubMed] [Google Scholar]
- Miller, R. H. (1996). Oligodendrocyte origins. Trends NeuroSci.19:92-96. [DOI] [PubMed] [Google Scholar]
- Mizuguchi, R., Sugimori, M., Takebayashi, H., Kosako, H., Nagao, M., Yoshida, S., Nabeshima, Y., Shimamura, K., and Nakafuku, M. (2001). Combinatorial roles of Olig2 and Neurogenin2 in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons. Neuron31:757-771. [DOI] [PubMed] [Google Scholar]
- Noble, M., Murray, K., Stroobant, P., Waterfield, M. D., and Riddle, P. (1988). Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature333:560-562. [DOI] [PubMed] [Google Scholar]
- Noll, E., and Miller, R. H. (1994). Regulation of oligodendrocyte differentiation: A role for retinoic acid in the spinal cord. Development120:649-660. [DOI] [PubMed] [Google Scholar]
- Novitch, B. G., Chen, A. I., and Jessell, T. M. (2001). Coordinate regulation of motor neuron subtype identity and pan-neuronal properties by the bHLH repressor Olig2. Neuron31:773-789. [DOI] [PubMed] [Google Scholar]
- Raff, M. C., Abney, E. R., and Fok-Seang, J. (1985). Reconstitution of a developmental clock In vitro: A critical role for astrocytes in the timing of oligodendrocyte differentiation. Cell42:61-69. [DOI] [PubMed] [Google Scholar]
- Raff, M. C., Lillien, L. E., Richardson, W. D., Burne, J. F., and Noble, M. D. (1988). Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture. Nature333:562-565. [DOI] [PubMed] [Google Scholar]
- Raff, M. C., Miller, R. H., and Noble, M. (1983). A glial progenitor cell that develops In vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature303:390-396. [DOI] [PubMed] [Google Scholar]
- Ranscht, B., Clapshaw, P. A., Price, J., Noble, M., and Seifert, W. (1982). Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside. Proc. Natl. Acad. Sci. U.S.A.79:2709-2713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott, M. P. (1992). Vertebrate homeobox gene nomenclature. Cell71:551-553. [DOI] [PubMed] [Google Scholar]
- Sommer, I., and Schachner, M. (1981). Monoclonal antibodies (O1 to O4) to oligodendrocyte cell surfaces: An immunocytological study in the central nervous system. Dev. Biol.83:311-327. [DOI] [PubMed] [Google Scholar]
- Sun, T., Pringle, N. P., Hardy, A. P., Richardson, W. D., and Smith, H. K. (1998). Pax6 influences the time and site of origin of glial precursors in the ventral neural tube. Mol. Cell. Neurosci.12:228-239. [DOI] [PubMed] [Google Scholar]
- Takebayashi, H., Yoshida, S., Sugimori, M., Kosako, H., Kominami, R., Nakafuku, M., and Nabeshima, Y. (2000). Dynamic expression of basic helix-loop-helix Olig family members: Implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3. Mech. Dev.99:143-148. [DOI] [PubMed] [Google Scholar]
- Tan, D.-P., Ferrante, J., Nazarali, A., Shao, X., Kozak, C. A., Guo, V., and Nirenberg, M. (1992). Murine Hox-1.11 homeobox gene structure and expression. Proc. Natl. Acad. Sci. U.S.A.89:6280-6284. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Theiler, K. (1972). The House Mouse; Development and Normal Stages From Fertilization to Four Weeks of Age, Springer, New York, pp. 168. [Google Scholar]
- Wang, S., Sdrulla, A., Johnson, J. E., Yokota, Y., and Barres, B. A. (2001). A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development. Neuron29:603-614. [DOI] [PubMed] [Google Scholar]
- Wolf, L. V., Yeung, J. M., Doucette, J. R., and Nazarali, A. J. (2001). Coordinated expression of Hoxa2, Hoxd1, and Pax6 in the developing diencephalon. NeuroReport12:329-333. [DOI] [PubMed] [Google Scholar]
- Zhou, Q., Wang, S., and Anderson, D. J. (2000). Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron [DOI] [PubMed]