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Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration.

Ashley McDonough1, Gina E Elsen1, Ray M Daza1,2

  • 1Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, United States.

Frontiers in Neuroscience
|January 25, 2021
PubMed
Summary

Transcription factor Tbr2 is crucial for the development of cerebellar unipolar brush cells (UBCs). Tbr2 deficiency impairs UBC migration and differentiation in mice, with similar developmental pathways observed in human cerebellum.

Keywords:
Tbr2cell migrationcerebellumdevelopmentunipolar brush cells

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Unipolar brush cells (UBCs) are cerebellar interneurons with specific expression of transcription factor Tbr2.
  • The precise role of Tbr2 in UBC development and morphology requires further investigation.

Purpose of the Study:

  • To elucidate the role of Tbr2 in the development and morphology of cerebellar UBCs.
  • To compare UBC development in mice and humans.

Main Methods:

  • Analysis of UBC morphology in Tbr2 reporter and lineage tracer mouse models.
  • Examination of Tbr2 conditional knock-out (cKO) mice to assess Tbr2 deficiency effects.
  • Study of Tbr2 expression in mid-gestational human cerebellum.

Main Results:

  • UBCs exhibit complex morphologies, including multiple and bifurcating dendrites, suggesting "dendritic brush cells" (DBCs) as a potential new term.
  • Tbr2 deficiency in cKO mice resulted in the complete absence of mature UBCs.
  • Impaired migration of UBC precursors from the rhombic lip to the cerebellar cortex was observed in Tbr2 cKO mice.
  • Tbr2+ UBC precursors in human cerebellum follow similar migration pathways and exhibit a characteristic "fountain-like" dispersal, mirroring rodent development.

Conclusions:

  • UBC migration and differentiation are highly sensitive to Tbr2 deficiency.
  • Tbr2 is essential for the proper development and maturation of UBCs.
  • UBC development is conserved between rodents and humans, highlighting the conserved role of Tbr2.