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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]
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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

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