TDP-43 is essential for Eph receptor-class-specific spinal motor axon trajectory into the limb.
Neurosci Res
; 176: 31-39, 2022 Mar.
Article
em En
| MEDLINE
| ID: mdl-34687812
ABSTRACT
During the neural circuit formation, neuronal growth cones must be guided precisely to their neuronal or muscle targets, which can be achieved by the activation of membrane-bound guidance receptors at the periphery. However, the mechanisms that regulate the temporal availability of these receptors remain largely unknown. TAR DNA binding protein-43 (TDP-43) has been proposed to bind with the mRNAs of guidance receptors, thus prompting us to investigate its role in axon guidance of the spinal lateral motor column (LMC) neurons into the limb mesenchyme. We first identified the TDP-43 expression in the LMC neurons at the stage of axons growth into the limb using in situ mRNA hybridization. The loss and gain of TDP-43 function in chick LMC neurons redirected their axon trajectory with opposite effects. In mice, a spinal motor neuron-specific TDP-43 deletion led to the misrouting of LMC axons. Further, ectopic TDP-43 expression increased EphB protein levels in LMC neurons, suggesting that TDP-43 mediates LMC pathfinding by regulating EphB expression. Finally, TDP-43 levels influenced the growth preference of LMC neurites against ephrin-B, but not Netrin-1 and Semaphorin ligands. Our results demonstrate that TDP-43 is essential for the ephrinBEphB signaling-mediated axon trajectory selection of LMC subtypes into the limb.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Axônios
/
Receptores da Família Eph
/
Proteínas de Ligação a DNA
Limite:
Animals
Idioma:
En
Revista:
Neurosci Res
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article