A Toll-receptor map underlies structural brain plasticity

Abstract

Experience alters brain structure, but the underlying mechanism remained unknown. Structural plasticity reveals that brain function is encoded in generative changes to cells that compete with destructive processes driving neurodegeneration. At an adult critical period, experience increases fiber number and brain size in Drosophila. Here, we asked if Toll receptors are involved. Tolls demarcate a map of brain anatomical domains. Focusing on Toll-2, loss of function caused apoptosis, neurite atrophy and impaired behaviour. Toll-2 gain of function and neuronal activity at the critical period increased cell number. Toll-2 induced cycling of adult progenitor cells via a novel pathway, that antagonized MyD88-dependent quiescence, and engaged Weckle and Yorkie downstream. Constant knock-down of multiple Tolls synergistically reduced brain size. Conditional over-expression of Toll-2 and wek at the adult critical period increased brain size. Through their topographic distribution, Toll receptors regulate neuronal number and brain size, modulating structural plasticity in the adult brain.

Polyploidy in the adult Drosophila brain

“…A population of about 40 adult neural progenitors has been reported in the optic lobe and a population of glial progenitors has been reported in the central brain ( Fernández-Hernández et al, 2013 ; Foo et al, 2017 ). Upon damage or cell loss, hallmarks of cycling have been shown to be activated, although the overall level of proliferation in the adult brain remains very low ( Crocker et al, 2020 ; Fernandez-Hernandez et al, 2019 ; Fernández-Hernández et al, 2013 ; Foo et al, 2017 ; Li et al, 2020 ). Thus, the brain of the adult fly is thought to be almost entirely postmitotic with most cells in G0 with a diploid (2C) DNA content.…”

Adult Neurogenesis in the Drosophila Brain: The Evidence and the Void

“…The presence of cycling cells in the adult brain was confirmed using other G1, S-phase and G2 markers, PCNA-GFP and FUCCI, at the adult critical period (up to five days post-eclosion). PCNA-GFP + cells were found in normal brains [ 6 ]. With FUCCI, degron fusion-proteins to tagged cell cycling proteins E2F-GFP and cyclin-B-RFP are degraded as cells enter S phase or G1, respectively [ 39 ] (see Figure 2 a).…”

“…Thus, FUCCI labels cells that are in G1, S, G2/M, or M/G1 phases of the cell cycle and does not label post-mitotic cells that are in G0 [ 39 ]. Control brains bearing the transgenes to visualise these markers but otherwise normal, also revealed the presence of FUCCI + cells in G1/S, G2 and G2/M, potentially undergoing mitosis [ 6 ]. Presence of cells cycling through G2/M was also visualised using GFP-tagged Cdc25/String (Stg), whch is expressed in G2 and triggers the G2/M transition [ 6 , 40 , 41 ].…”

“…Control brains bearing the transgenes to visualise these markers but otherwise normal, also revealed the presence of FUCCI + cells in G1/S, G2 and G2/M, potentially undergoing mitosis [ 6 ]. Presence of cells cycling through G2/M was also visualised using GFP-tagged Cdc25/String (Stg), whch is expressed in G2 and triggers the G2/M transition [ 6 , 40 , 41 ]. Accordingly, proliferating cells exist in the Drosophila adult brain, and most prominently at the critical period between 1 and 6 days post-eclosion [ 6 , 34 , 37 ].…”

“…Acquiring evidence of adult neurogenesis is technically challenging. Both in mammals (including humans) and in invertebrates, evidence has generally relied on cell cycle and lineage tracing markers, such as 5-Bromo-2-deoxyuridine (BrdU), and neural stem cell markers [ 1 , 2 , 3 , 4 , 5 , 6 ]. However, the ability to detect these markers could depend on exactly how experiments were carried out, and as a result, disparate findings have been feeding the controversy [ 1 ].…”