Brn3a controls the soma localization and axonal extension patterns of developing spinal dorsal horn neurons

PLoS One. 2023 Sep 21;18(9):e0285295. doi: 10.1371/journal.pone.0285295. eCollection 2023.

Abstract

The spinal dorsal horn comprises heterogeneous neuronal populations, that interconnect with one another to form neural circuits modulating various types of sensory information. Decades of evidence has revealed that transcription factors expressed in each neuronal progenitor subclass play pivotal roles in the cell fate specification of spinal dorsal horn neurons. However, the development of subtypes of these neurons is not fully understood in more detail as yet and warrants the investigation of additional transcription factors. In the present study, we examined the involvement of the POU domain-containing transcription factor Brn3a in the development of spinal dorsal horn neurons. Analyses of Brn3a expression in the developing spinal dorsal horn neurons in mice demonstrated that the majority of the Brn3a-lineage neurons ceased Brn3a expression during embryonic stages (Brn3a-transient neurons), whereas a limited population of them continued to express Brn3a at high levels after E18.5 (Brn3a-persistent neurons). Loss of Brn3a disrupted the localization pattern of Brn3a-persistent neurons, indicating a critical role of this transcription factor in the development of these neurons. In contrast, Brn3a overexpression in Brn3a-transient neurons directed their localization in a manner similar to that in Brn3a-persistent neurons. Moreover, Brn3a-overexpressing neurons exhibited increased axonal extension to the ventral and ventrolateral funiculi, where the axonal tracts of Brn3a-persistent neurons reside. These results suggest that Brn3a controls the soma localization and axonal extension patterns of Brn3a-persistent spinal dorsal horn neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons
  • Cell Differentiation
  • Mice
  • Neurons*
  • Posterior Horn Cells*
  • Transcription Factors / genetics

Substances

  • Transcription Factors
  • Pou4f1 protein, mouse

Grants and funding

This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number JP 19K07855, JP 22K07383, JP 16H06276 (AdAMS), and Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, si Inovarii Grant Number PN-III-P4-PCE-2021-0333. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.