The transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor plate development and commissural axon guidance.

2.50
Hdl Handle:
http://hdl.handle.net/10033/136135
Title:
The transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor plate development and commissural axon guidance.
Authors:
Holz, Andreas; Kollmus, Heike; Ryge, Jesper; Niederkofler, Vera; Dias, Jose; Ericson, Johan; Stoeckli, Esther T; Kiehn, Ole; Arnold, Hans-Henning
Abstract:
The transcription factors Nkx2.2 and Nkx2.9 have been proposed to execute partially overlapping functions in neuronal patterning of the ventral spinal cord in response to graded sonic hedgehog signaling. The present report shows that in mice lacking both Nkx2 proteins, the presumptive progenitor cells in the p3 domain of the neural tube convert to motor neurons (MN) and never acquire the fate of V3 interneurons. This result supports the concept that Nkx2 transcription factors are required to establish V3 progenitor cells by repressing the early MN lineage-specific program, including genes like Olig2. Nkx2.2 and Nkx2.9 proteins also perform an additional, hitherto unknown, function in the development of non-neuronal floor plate cells. Here, we demonstrate that loss of both Nkx2 genes results in an anatomically smaller and functionally impaired floor plate causing severe defects in axonal pathfinding of commissural neurons. Defective floor plates were also seen in Nkx2.2(+/-);Nkx2.9(-/-) compound mutants and even in single Nkx2.9(-/-) mutants, suggesting that floor plate development is sensitive to dose and/or timing of Nkx2 expression. Interestingly, adult Nkx2.2(+/-);Nkx2.9(-/-) compound-mutant mice exhibit abnormal locomotion, including a permanent or intermittent hopping gait. Drug-induced locomotor-like activity in spinal cords of mutant neonates is also affected, demonstrating increased variability of left-right and flexor-extensor coordination. Our data argue that the Nkx2.2 and Nkx2.9 transcription factors contribute crucially to the formation of neuronal networks that function as central pattern generators for locomotor activity in the spinal cord. As both factors affect floor plate development, control of commissural axon trajectories might be the underlying mechanism.
Affiliation:
Cell and Molecular Biology, University of Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany.
Citation:
The transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor plate development and commissural axon guidance. 2010, 137 (24):4249-60 Development
Journal:
Development (Cambridge, England)
Issue Date:
Dec-2010
URI:
http://hdl.handle.net/10033/136135
DOI:
10.1242/dev.053819
PubMed ID:
21068056
Type:
Article
Language:
en
ISSN:
1477-9129
Appears in Collections:
publications of the department infection genetics (INFG)

Full metadata record

DC FieldValue Language
dc.contributor.authorHolz, Andreasen
dc.contributor.authorKollmus, Heikeen
dc.contributor.authorRyge, Jesperen
dc.contributor.authorNiederkofler, Veraen
dc.contributor.authorDias, Joseen
dc.contributor.authorEricson, Johanen
dc.contributor.authorStoeckli, Esther Ten
dc.contributor.authorKiehn, Oleen
dc.contributor.authorArnold, Hans-Henningen
dc.date.accessioned2011-07-15T14:21:44Z-
dc.date.available2011-07-15T14:21:44Z-
dc.date.issued2010-12-
dc.identifier.citationThe transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor plate development and commissural axon guidance. 2010, 137 (24):4249-60 Developmenten
dc.identifier.issn1477-9129-
dc.identifier.pmid21068056-
dc.identifier.doi10.1242/dev.053819-
dc.identifier.urihttp://hdl.handle.net/10033/136135-
dc.description.abstractThe transcription factors Nkx2.2 and Nkx2.9 have been proposed to execute partially overlapping functions in neuronal patterning of the ventral spinal cord in response to graded sonic hedgehog signaling. The present report shows that in mice lacking both Nkx2 proteins, the presumptive progenitor cells in the p3 domain of the neural tube convert to motor neurons (MN) and never acquire the fate of V3 interneurons. This result supports the concept that Nkx2 transcription factors are required to establish V3 progenitor cells by repressing the early MN lineage-specific program, including genes like Olig2. Nkx2.2 and Nkx2.9 proteins also perform an additional, hitherto unknown, function in the development of non-neuronal floor plate cells. Here, we demonstrate that loss of both Nkx2 genes results in an anatomically smaller and functionally impaired floor plate causing severe defects in axonal pathfinding of commissural neurons. Defective floor plates were also seen in Nkx2.2(+/-);Nkx2.9(-/-) compound mutants and even in single Nkx2.9(-/-) mutants, suggesting that floor plate development is sensitive to dose and/or timing of Nkx2 expression. Interestingly, adult Nkx2.2(+/-);Nkx2.9(-/-) compound-mutant mice exhibit abnormal locomotion, including a permanent or intermittent hopping gait. Drug-induced locomotor-like activity in spinal cords of mutant neonates is also affected, demonstrating increased variability of left-right and flexor-extensor coordination. Our data argue that the Nkx2.2 and Nkx2.9 transcription factors contribute crucially to the formation of neuronal networks that function as central pattern generators for locomotor activity in the spinal cord. As both factors affect floor plate development, control of commissural axon trajectories might be the underlying mechanism.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshBody Patterningen
dc.subject.meshEmbryo, Mammalianen
dc.subject.meshHomeodomain Proteinsen
dc.subject.meshImmunohistochemistryen
dc.subject.meshIn Situ Hybridizationen
dc.subject.meshMiceen
dc.subject.meshMice, Mutant Strainsen
dc.subject.meshNeural Tubeen
dc.subject.meshSpinal Corden
dc.subject.meshStem Cellsen
dc.subject.meshTranscription Factorsen
dc.titleThe transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor plate development and commissural axon guidance.en
dc.typeArticleen
dc.contributor.departmentCell and Molecular Biology, University of Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany.en
dc.identifier.journalDevelopment (Cambridge, England)en

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