MECHANO-SENSORY REGULATION BY TRPM7 IN CORTICAL INTERNEURON MIGRATION DURING NEURODEVELOPMENT adeyemisolomon20@gmail.com

 

MECHANO-SENSORY REGULATION BY TRPM7 IN CORTICAL INTERNEURON MIGRATION DURING NEURODEVELOPMENT

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Nigeria

Oral or Poster

The precise migration of cortical interneurons is essential for proper cortical circuit formation. TRPM7, a mechanosensitive channel-kinase, has been implicated in cellular motility, yet its specific role in cortical interneuron migration remains unclear.

To investigate TRPM7’s role, we utilized a conditional knockout model by crossing TRPM7^flox/flox mice with Dlx5/6-Cre-IRES-mCherry mice, enabling selective deletion in interneuron precursors. Embryonic medial ganglionic eminence (MGE) explants were cultured, and time-lapse imaging captured interneuron motility. Genotypes included wild type, TRPM7^flox/+, and TRPM7^flox/flox. Quantitative analyses assessed maximum velocity, net displacement, and trajectory organization across groups.

While no statistically significant difference was observed in maximum velocity, wild-type interneurons exhibited broader high-velocity distributions. In contrast, directional migration was markedly disrupted in TRPM7^flox/flox cells, with significant reductions in net displacement and highly randomized trajectories. A dose-dependent decline in directional efficiency was evident: Wild type > flox/+ > flox/flox. These findings suggest TRPM7 is essential for maintaining directional fidelity rather than general motility.

TRPM7 regulates the directionality and consistency of cortical interneuron migration during neurodevelopment, likely through mechanosensory pathways. Its deficiency disrupts targeted migration, which may contribute to the etiology of neurodevelopmental disorders such as epilepsy, autism, or schizophrenia. Further exploration into TRPM7-mediated signaling may uncover novel therapeutic strategies for restoring interneuron positioning and circuit formation.