prpf4 is essential for cell survival and posterior lateral line primordium migration in zebrafish

Yixia Wang1, Yanchao Han1, Pengfei Xu1

  • 1State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Insights

Pre-mRNA processing factor 4 (Prpf4) is vital for neural cell survival and migration in zebrafish. Its deficiency disrupts spliceosome function, leading to apoptosis and developmental defects.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Pre-mRNA processing factor 4 (Prpf4) is a crucial spliceosome component.
  • Mutations in Prpf4 are linked to retinitis pigmentosa.
  • Zebrafish prpf4t243 mutant harbors a Tol2 transposon gene trap.

Purpose of the Study:

  • To characterize the function of Prpf4 in zebrafish development.
  • To investigate the role of Prpf4 in neural cell survival and migration.
  • To understand the molecular mechanisms underlying Prpf4 deficiency.

Main Methods:

  • Zebrafish prpf4t243 mutant characterization.
  • Analysis of apoptosis in neural cells.
  • Assessment of posterior lateral line primordial (pLLP) cell survival and migration.
  • RNA-sequencing (RNA-Seq) analysis.

Main Results:

  • prpf4t243 mutants exhibit p53-dependent apoptosis in brain and spinal cord cells.
  • Prpf4 is essential for pLLP cell survival and migration.
  • Prpf4 deficiency perturbs Fgf, Wnt/β-catenin, and chemokine signaling pathways.
  • RNA-Seq reveals impaired spliceosome assembly and altered pre-mRNA splicing.

Conclusions:

  • Prpf4 plays an essential role in pre-mRNA splicing and neural cell survival.
  • Prpf4 is critical for posterior lateral line primordial cell migration.
  • Prpf4 deficiency impacts multiple signaling pathways and spliceosome function.

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