A Toll-receptor map underlies structural brain plasticity.

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Experience-dependent structural plasticity modifies brain architecture.
• The molecular mechanisms underlying adult brain structural changes and neurogenesis remain largely unknown.
• Toll receptors are known to map brain anatomical domains.

Purpose of the Study:

• To investigate the role of Toll receptors in adult brain structural plasticity in Drosophila.
• To elucidate the molecular pathways involved in experience-induced brain growth.

Main Methods:

• Genetic manipulation of Toll receptors (loss-of-function, gain-of-function, knock-down, conditional over-expression) in Drosophila.
• Analysis of cell apoptosis, neurite morphology, cell proliferation, and behavior.
• Investigation of downstream signaling pathways involving MyD88, Weckle, and Yorkie.

Main Results:

• Loss of Toll-2 function led to apoptosis, neurite atrophy, and impaired behavior.
• Toll-2 gain-of-function and neuronal activity increased cell number during the critical period.
• Toll-2 induced adult progenitor cell cycling via a novel pathway, antagonizing MyD88-dependent quiescence.
• Simultaneous knock-down of multiple Tolls synergistically reduced brain size.
• Conditional over-expression of Toll-2 and weck increased brain size.

Conclusions:

• Toll receptors, through their topographic distribution, regulate neuronal number and brain size.
• Toll signaling modulates structural plasticity in the adult Drosophila brain.
• A novel Toll-2 pathway involving Weckle and Yorkie promotes adult neurogenesis and brain growth.