Developmental switch in NF-kappaB signalling required for neurite growth

Area of Science:

• Cellular signaling
• Neuroscience
• Developmental biology

Background:

• Extracellular signals induce specific intracellular signaling patterns for cell-type specific responses.
• Intracellular signaling networks exhibit plasticity, but developmental switches for identical responses to the same signal are rare.

Purpose of the Study:

• To investigate the developmental switch in intracellular signaling networks for BDNF-promoted neurite growth in mouse sensory neurons.
• To identify changes in NF-kappaB signaling mechanisms and p65 subunit phosphorylation status before and after birth.

Main Methods:

• Comparative analysis of NF-kappaB activation mechanisms in foetal and postnatal mouse sensory neurons.
• Investigation of IkappaBalpha phosphorylation and p65 subunit phosphorylation status.
• Assessment of the role of Src family kinases in NF-kappaB activation.

Main Results:

• NF-kappaB signaling is essential for BDNF-promoted neurite growth in both foetal and postnatal sensory neurons.
• A switch in NF-kappaB activation occurs around birth, involving different phosphorylation events of IkappaBalpha and p65.
• Foetal neurons utilize atypical BDNF-activated NF-kappaB via tyrosine phosphorylation of IkappaBalpha and p65 dephosphorylation; postnatal neurons use BDNF-independent constitutive activation via serine phosphorylation of IkappaBalpha and p65 dephosphorylation.

Conclusions:

• An abrupt developmental switch in NF-kappaB signaling occurs in mouse sensory neurons, altering activation mechanisms for the same cellular response (neurite growth).
• This switch demonstrates significant plasticity in intracellular signaling networks, even in highly differentiated cells.
• The findings reveal novel insights into developmental regulation of neuronal growth and signaling pathways.