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Neph1 is required for neurite branching and is negatively regulated by the PRRXL1 homeodomain factor in the developing spinal cord dorsal horn.
Baltar, João; Miranda, Rafael Mendes; Cabral, Maria; Rebelo, Sandra; Grahammer, Florian; Huber, Tobias B; Reguenga, Carlos; Monteiro, Filipe Almeida.
Affiliation
  • Baltar J; Unidade de Biologia Experimental, Departamento de Biomedicina, FMUP - Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
  • Miranda RM; Pain Neurobiology, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal.
  • Cabral M; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Rebelo S; Unidade de Biologia Experimental, Departamento de Biomedicina, FMUP - Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
  • Grahammer F; Pain Neurobiology, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal.
  • Huber TB; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Reguenga C; Unidade de Biologia Experimental, Departamento de Biomedicina, FMUP - Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
  • Monteiro FA; Pain Neurobiology, IBMC - Instituto de Biologia Celular e Molecular, Porto, Portugal.
Neural Dev ; 19(1): 13, 2024 Jul 24.
Article in En | MEDLINE | ID: mdl-39049046
ABSTRACT
The cell-adhesion molecule NEPH1 is required for maintaining the structural integrity and function of the glomerulus in the kidneys. In the nervous system of Drosophila and C. elegans, it is involved in synaptogenesis and axon branching, which are essential for establishing functional circuits. In the mammalian nervous system, the expression regulation and function of Neph1 has barely been explored. In this study, we provide a spatiotemporal characterization of Neph1 expression in mouse dorsal root ganglia (DRGs) and spinal cord. After the neurogenic phase, Neph1 is broadly expressed in the DRGs and in their putative targets at the dorsal horn of the spinal cord, comprising both GABAergic and glutamatergic neurons. Interestingly, we found that PRRXL1, a homeodomain transcription factor that is required for proper establishment of the DRG-spinal cord circuit, prevents a premature expression of Neph1 in the superficial laminae of the dorsal spinal cord at E14.5, but has no regulatory effect on the DRGs or on either structure at E16.5. By chromatin immunoprecipitation analysis of the dorsal spinal cord, we identified four PRRXL1-bound regions within the Neph1 introns, suggesting that PRRXL1 directly regulates Neph1 transcription. We also showed that Neph1 is required for branching, especially at distal neurites. Together, our work showed that Prrxl1 prevents the early expression of Neph1 in the superficial dorsal horn, suggesting that Neph1 might function as a downstream effector gene for proper assembly of the DRG-spinal nociceptive circuit.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription Factors / Neurites / Homeodomain Proteins / Spinal Cord Dorsal Horn / Ganglia, Spinal Limits: Animals Language: En Journal: Neural Dev Year: 2024 Document type: Article Affiliation country: Portugal

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription Factors / Neurites / Homeodomain Proteins / Spinal Cord Dorsal Horn / Ganglia, Spinal Limits: Animals Language: En Journal: Neural Dev Year: 2024 Document type: Article Affiliation country: Portugal