DOI: 10.4103/ijamr.ijamr_132_25 ISSN: 2349-4220

Stage-dependent Expression of Wnt/β-catenin Pathway Components during Oligodendrocyte Differentiation In vitro

Debadrita Basak, Rajarshi Kar, Edelbert Anthonio Almeida, Sudip Sen, Diwesh Chawla, Sagar Tyagi, Mohit Mehndiratta, Seema Garg
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Abstract

Background:

In preterm infants, white matter injury is characterized by defective myelination, mainly due to arrested differentiation of premyelinating oligodendrocytes, rather than their depletion due to cell death. Multiple intracellular signaling pathways regulate oligodendrocyte maturation. Out of these, the Wnt/β-catenin pathway, though extensively studied, remains controversial, particularly with respect to its stage-specific role in human oligodendrocyte development.

Methods:

The MO3.13 cell line was used as an in vitro model to study oligodendrocyte maturation induced by phorbol-12-myristate-13-acetate (PMA). Morphological changes were observed and recorded. The messenger ribonucleic acid expression of key components of the Wnt/β-catenin pathway (β-catenin, T-cell factor-4 [TCF4], and lymphoid enhancer-binding factor-1 [LEF1]), along with the downstream transcription factor SOX10 and the myelination-associated marker myelin basic protein (MBP), was assessed on day 0, 3, 5, and 7, using quantitative real-time polymerase chain reaction.

Results:

PMA treatment brought about morphological changes consistent with oligodendrocyte maturation, accompanied by a progressive increase in MBP expression. The expression of Wnt/β-catenin pathway components demonstrated stage-dependent transcriptional changes, with an initial reduction during early differentiation followed by increased expression at later stages.

Conclusion:

This study demonstrates a time-dependent association between the expression of Wnt/β-catenin pathway components and oligodendrocyte maturation in a human cell-based in vitro model. The findings underscore the importance of considering developmental stage and timing when interpreting the role of Wnt signaling in oligodendrocyte differentiation. Further mechanistic and in vivo studies are required to elucidate the functional significance of these observations.

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