Inhibition of TrkB- and TrkC-Signaling Pathways Affects Neurogenesis in the Opossum Developing Neocortex

K Bartkowska1, B Tepper1, A Gawda1

  • 1Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.

Insights

Neurotrophin signaling via TrkB and TrkC receptors is crucial for neocortical progenitor cell proliferation and neuron migration in vivo. Their activity regulates cell division rates and the two-step migration of neurons to the subplate zone.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • TrkB and TrkC signaling pathways influence neurogenesis in vitro.
  • Neocortical development involves complex processes of progenitor cell proliferation, differentiation, survival, and migration.

Purpose of the Study:

  • To investigate the in vivo role of TrkB and TrkC signaling in neocortical progenitor cell populations during development.
  • To determine if TrkB and TrkC signaling affect progenitor cell proliferation, differentiation, survival, and neuron migration in the Monodelphis opossum.

Main Methods:

  • Inhibition of TrkB and TrkC signaling pathways in vivo within the developing neocortex of Monodelphis opossum.
  • Analysis of progenitor cell proliferation, differentiation, apoptosis, and neuron migration to the subplate zone.

Main Results:

  • Inhibition of TrkB and TrkC signaling affected progenitor cell proliferation, with TrkC showing a more significant impact on cell division rates.
  • Unlike in vitro findings, TrkB and TrkC inhibition did not alter apoptosis in vivo.
  • Disruption of TrkB and TrkC signaling led to the arrest of newly generated neurons, preventing their penetration of the subplate zone.

Conclusions:

  • TrkB and TrkC signaling are essential for regulating progenitor cell proliferation and the rate of cell division during neocortex formation.
  • Neuron migration appears to be a two-step process, with TrkB and TrkC signaling specifically regulating the second step of migration to the final position within the subplate.
  • The in vivo functions of TrkB and TrkC in neocortical development differ from their roles observed in primary cell cultures, particularly concerning apoptosis.

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