The transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor plate development and commissural axon guidance.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Stoeckli, Esther T
MetadataShow full item record
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.
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 Development
AffiliationCell and Molecular Biology, University of Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany.
JournalDevelopment (Cambridge, England)
The following license files are associated with this item:
- Nato3 plays an integral role in dorsoventral patterning of the spinal cord by segregating floor plate/p3 fates via Nkx2.2 suppression and Foxa2 maintenance.
- Authors: Mansour AA, Khazanov-Zisman S, Netser Y, Klar A, Ben-Arie N
- Issue date: 2014 Feb
- Sp8 plays a supplementary role to Pax6 in establishing the pMN/p3 domain boundary in the spinal cord.
- Authors: Li X, Liu Z, Qiu M, Yang Z
- Issue date: 2014 Jul
- Tcf/Lef repressors differentially regulate Shh-Gli target gene activation thresholds to generate progenitor patterning in the developing CNS.
- Authors: Wang H, Lei Q, Oosterveen T, Ericson J, Matise MP
- Issue date: 2011 Sep
- Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling.
- Authors: Briscoe J, Sussel L, Serup P, Hartigan-O'Connor D, Jessell TM, Rubenstein JL, Ericson J
- Issue date: 1999 Apr 15
- Homozygous Ft embryos are affected in floor plate maintenance and ventral neural tube patterning.
- Authors: Götz K, Briscoe J, Rüther U
- Issue date: 2005 Jun