Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-25T16:03:12.279Z Has data issue: false hasContentIssue false
  • English
  • Français

nkx2.2a promotes specification and differentiation of a myelinating subset of oligodendrocyte lineage cells in zebrafish

Published online by Cambridge University Press:  08 September 2009

Sarah Kucenas ,
Heather Snell  and
Bruce Appel
Sarah Kucenas
Affiliation:
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA
Heather Snell
Affiliation:
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA
Bruce Appel*
Affiliation:
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA Department of Pediatrics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
*
Correspondence should be addressed to: Bruce Appel, Department of Pediatrics, University of Colorado Denver, Anschutz Medical Campus, Mail Stop 8108, Aurora, CO 80045, USA phone: (303) 724-3465 email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

During development, multipotent neural precursors give rise to oligodendrocyte progenitor cells (OPCs), which migrate and divide to produce additional OPCs. Near the end of embryogenesis and during postnatal stages, many OPCs stop dividing and differentiate as myelinating oligodendrocytes, whereas others persist as nonmyelinating cells. Investigations of oligodendrocyte development in mice indicated that the Nkx2.2 transcription factor both limits the number of OPCs that are formed and subsequently promotes their differentiation, raising the possibility that Nkx2.2 plays a key role in determining myelinating versus nonmyelinating fate. We used in vivo time-lapse imaging and loss-of-function experiments in zebrafish to further explore formation and differentiation of oligodendrocyte lineage cells. Our data show that newly specified OPCs are heterogeneous with respect to gene expression and fate. Whereas some OPCs express the nkx2.2a gene and differentiate as oligodendrocytes, others that do not express nkx2.2a mostly remain as nonmyelinating OPCs. Similarly to mouse, loss of nkx2.2a function results in excess OPCs and delayed oligodendrocyte differentiation. Notably, excess OPCs are formed as a consequence of prolonged OPC production from neural precursor cells. We conclude that Nkx2.2 promotes timely specification and differentiation of myelinating oligodendrocyte lineage cells from species representing different vertebrate taxa.

Keywords

Olig2zebrafishneural precursorsglia
Type
Research Article
Information
Neuron Glia Biology , Volume 4 , Issue 2 , May 2008 , pp. 71 - 81
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Barth, K.A. and Wilson, S.W. (1995) Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain. Development 121, 1755–1768.CrossRefGoogle ScholarPubMed
Baumann, N. and Pham-Dinh, D. (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiological Review 81, 871–927.CrossRefGoogle ScholarPubMed
Bradel, E.J. and Prince, F.P. (1983) Cultured neonatal rat oligodendrocytes elaborate myelin membrane in the absence of neurons. Journal of Neuroscience Research 9, 381–392.CrossRefGoogle ScholarPubMed
Briscoe, J., Pierani, A., Jessell, T.M. and Ericson, J. (2000) A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell 101, 435–445.CrossRefGoogle ScholarPubMed
Briscoe, J., Sussel, L., Serup, P., Hartigan-O'Connor, D., Jessell, T.M., Rubenstein, J.L. et al. (1999) Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature 398, 622–627.CrossRefGoogle ScholarPubMed
Brosamle, C. and Halpern, M.E. (2002) Characterization of myelination in the developing zebrafish. Glia 39, 47–57.CrossRefGoogle ScholarPubMed
Dickinson, P.J., Fanarraga, M.L., Griffiths, I.R., Barrie, J.M., Kyriakides, E. and Montague, P. (1996) Oligodendrocyte progenitors in the embryonic spinal cord express DM-20. Neuropathology and Applied Neurobiology 22, 188–198.CrossRefGoogle ScholarPubMed
Dubois-Dalcq, M., Behar, T., Hudson, L. and Lazzarini, R.A. (1986) Emergence of three myelin proteins in oligodendrocytes cultured without neurons. Journal of Cell Biology 102, 384–392.CrossRefGoogle ScholarPubMed
Eaton, R.C., Lee, R.K. and Foreman, M.B. (2001) The Mauthner cell and other identified neurons of the brainstem escape network of fish. Progress in Neurobiology 63, 467–485.CrossRefGoogle Scholar
Ericson, J., Rashbass, P., Schedl, A., Brenner-Morton, S., Kawakami, A., van Heyningen, V. et al. (1997) Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell 90, 169–180.CrossRefGoogle ScholarPubMed
Fu, H., Cai, J., Rutledge, M., Hu, X. and Qiu, M. (2003) Oligodendrocytes can be generated from the local ventricular and subventricular zones of embryonic chicken midbrain. Brain Research. Developmental Brain Research 143, 161–165.CrossRefGoogle ScholarPubMed
Fu, H., Qi, Y., Tan, M., Cai, J., Takebayashi, H., Nakafuku, M. et al. (2002) Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte differentiation. Development 129, 681–693.CrossRefGoogle ScholarPubMed
Hartline, D.K. and Colman, D.R. (2007) Rapid conduction and the evolution of giant axons and myelinated fibers. Current Biology 17, R29–R35.CrossRefGoogle ScholarPubMed
Hauptmann, G. and Gerster, T. (2000) Multicolor whole-mount in situ hybridization. Methods of Molecular Biology 137, 139–148.Google ScholarPubMed
Kirby, B.B., Takada, N., Latimer, A.J., Shin, J., Carney, T.J., Kelsh, R.N. et al. (2006) In vivo time-lapse imaging shows dynamic oligodendrocyte progenitor behavior during zebrafish development. Nature Neuroscience 9, 1506–1511.CrossRefGoogle ScholarPubMed
Korn, H. and Faber, D.S. (2005) The Mauthner cell half a century later: a neurobiological model for decision-making? Neuron 47, 13–28.CrossRefGoogle Scholar
Kucenas, S., Takada, N., Park, H.C., Woodruff, E., Broadie, K. and Appel, B. (2008) CNS-derived glia ensheath peripheral nerves and mediate motor root development. Nature Neuroscience 11, 143–151.CrossRefGoogle ScholarPubMed
Lewis, K.E. and Eisen, J.S. (2003) From cells to circuits: development of the zebrafish spinal cord. Progress in Neurobiology 69, 419–449.CrossRefGoogle ScholarPubMed
Liu, Y. and Rao, M.S. (2004) Olig genes are expressed in a heterogeneous population of precursor cells in the developing spinal cord. Glia 45, 67–74.CrossRefGoogle Scholar
Lu, Q.R., Sun, T., Zhu, Z., Ma, N., Garcia, M., Stiles, C.D. et al. (2002) Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109, 75–86.CrossRefGoogle ScholarPubMed
Miller, R.H. (2002) Regulation of oligodendrocyte development in the vertebrate CNS. Progress in Neurobiology 67, 451–467.CrossRefGoogle ScholarPubMed
Mirsky, R., Winter, J., Abney, E.R., Pruss, R.M., Gavrilovic, J. and Raff, M.C. (1980) Myelin-specific proteins and glycolipids in rat Schwann cells and oligodendrocytes in culture. Journal of Cell Biology 84, 483–494.CrossRefGoogle ScholarPubMed
Mizuguchi, R., Sugimori, M., Takebayashi, H., Kosako, H., Nagao, M., Yoshida, S. et al. (2001) Combinatorial roles of olig2 and neurogenin2 in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons. Neuron 31, 757–771.CrossRefGoogle ScholarPubMed
Nishiyama, A., Chang, A. and Trapp, B.D. (1999) NG2+ glial cells: a novel glial cell population in the adult brain. Journal of Neuropathology and Experimental Neurology 58, 1113–1124.CrossRefGoogle ScholarPubMed
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. Neuron 31, 773–789.CrossRefGoogle ScholarPubMed
Park, H., Mehta, A., Richardson, J.S. and Appel, B. (2002) olig2 is required for zebrafish primary motor neuron and oligodendrocyte development. Developmental Biology 248, 356–368.CrossRefGoogle ScholarPubMed
Park, H.C., Boyce, J., Shin, J. and Appel, B. (2005) Oligodendrocyte specification in zebrafish requires notch-regulated cyclin-dependent kinase inhibitor function. Journal of Neuroscience 25, 6836–6844.CrossRefGoogle ScholarPubMed
Park, H.C., Shin, J., Roberts, R.K. and Appel, B. (2007) An olig2 reporter gene marks oligodendrocyte precursors in the postembryonic spinal cord of zebrafish. Developmental Dynamics 236, 3402–3407.CrossRefGoogle ScholarPubMed
Peyron, F., Timsit, S., Thomas, J.L., Kagawa, T., Ikenaka, K. and Zalc, B. (1997) In situ expression of PLP/DM-20, MBP, and CNP during embryonic and postnatal development of the jimpy mutant and of transgenic mice overexpressing PLP. Journal of Neuroscience Research 50, 190–201.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Pogoda, H.M., Sternheim, N., Lyons, D.A., Diamond, B., Hawkins, T.A., Woods, I.G. et al. (2006) A genetic screen identifies genes essential for development of myelinated axons in zebrafish. Developmental Biology 298, 118–131.CrossRefGoogle ScholarPubMed
Qi, Y., Cai, J., Wu, Y., Wu, R., Lee, J., Fu, H. et al. (2001) Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. Development 128, 2723–2733.CrossRefGoogle ScholarPubMed
Rowitch, D.H. (2004) Glial specification in the vertebrate neural tube. Nature Reviews in Neuroscience 5, 409–419.CrossRefGoogle ScholarPubMed
Schafer, M., Kinzel, D., Neuner, C., Schartl, M., Volff, J.N. and Winkler, C. (2005) Hedgehog and retinoid signalling confines nkx2.2b expression to the lateral floor plate of the zebrafish trunk. Mechanics Development 122, 43–56.CrossRefGoogle Scholar
Schafer, M., Kinzel, D. and Winkler, C. (2007) Discontinuous organization and specification of the lateral floor plate in zebrafish. Developmental Biology 301, 117–129.CrossRefGoogle ScholarPubMed
Soula, C., Danesin, C., Kan, P., Grob, M., Poncet, C. and Cochard, P. (2001) Distinct sites of origin of oligodendrocytes and somatic motoneurons in the chick spinal cord: oligodendrocytes arise from Nkx2.2-expressing progenitors by a Shh-dependent mechanism. Development 128, 1369–1379.CrossRefGoogle ScholarPubMed
Sun, T., Echelard, Y., Lu, R., Yuk, D.I., Kaing, S., Stiles, C.D. et al. (2001) Olig bHLH proteins interact with homeodomain proteins to regulate cell fate acquisition in progenitors of the ventral neural tube. Current Biology 11, 1413–1420.CrossRefGoogle ScholarPubMed
Timsit, S., Martinez, S., Allinquant, B., Peyron, F., Puelles, L. and Zalc, B. (1995) Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression. Journal of Neuroscience 15, 1012–1024.CrossRefGoogle Scholar
Trapp, B.D., Moench, T., Pulley, M., Barbosa, E., Tennekoon, G. and Griffin, J. (1987) Spatial segregation of mRNA encoding myelin-specific proteins. Proceedings of the National Academy of Sciences U.S.A. 84, 7773–7777.CrossRefGoogle ScholarPubMed
Wolswijk, G. and Noble, M. (1989) Identification of an adult-specific glial progenitor cell. Development 105, 387–400.CrossRefGoogle ScholarPubMed
Xu, X., Cai, J., Fu, H., Wu, R., Qi, Y., Modderman, G. et al. (2000) Selective expression of Nkx-2.2 transcription factor in chicken oligodendrocyte progenitors and implications for the embryonic origin of oligodendrocytes. Molecular Cell and Neuroscience 16, 740–753.CrossRefGoogle ScholarPubMed
Zeller, N.K., Behar, T.N., Dubois-Dalcq, M.E. and Lazzarini, R.A. (1985) The timely expression of myelin basic protein gene in cultured rat brain oligodendrocytes is independent of continuous neuronal influences. Journal of Neuroscience 5, 2955–2962.CrossRefGoogle ScholarPubMed
Zhou, Q., Choi, G. and Anderson, D.J. (2001) The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2. Neuron 31, 791–807.CrossRefGoogle ScholarPubMed
Supplementary material: File

Kucenas and Appel supplementary material

Supplementary table 1

Download Kucenas and Appel supplementary material(File)
File 48.1 KB

Kucenas video 1

Kucenas video 1

Download Kucenas video 1(Video)
Video 7.6 MB
Supplementary material: PDF

Kucenas and Appel supplementary material

Supplementary table 4

Download Kucenas and Appel supplementary material(PDF)
PDF 42 KB
Supplementary material: Image

Kucenas and Appel supplementary material

Supplemental figure 1

Download Kucenas and Appel supplementary material(Image)
Image 1.6 MB
Supplementary material: File

Kucenas and Appel supplementary material

Supplementary table 2

Download Kucenas and Appel supplementary material(File)
File 43.5 KB

Kucenas video 2

Kucenas video 2

Download Kucenas video 2(Video)
Video 4.4 MB
Supplementary material: File

Kucenas and Appel supplementary material

Supplementary table 3

Download Kucenas and Appel supplementary material(File)
File 46.1 KB

Kucenas video 3

Kucenas video 3

Download Kucenas video 3(Video)
Video 13.1 MB

Kucenas video 4

Kucenas video 4

Download Kucenas video 4(Video)
Video 3.4 MB