Author response: Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila
Year: 2013
Type: peer-review
Abstract: The brains of all members of a species are similar, but not identical, and these differences are partly responsible for the range of behaviors displayed by individuals. The development of the nervous system is known to depend on the Notch signaling pathway, but the mechanisms that regulate the balance between fixed patterns of neuronal connectivity vs individual variability are largely unknown. Notch proteins are transmembrane proteins, which means that they have one part inside the cell membrane and another outside the cell. When a ligand protein—such as a Delta ligand—binds to the part that is outside the cell, the Notch protein breaks in two and the part inside the cell travels to the nucleus, where it can influence the expression of genes. Cells are selected to become neurons through a process known as mutual, or lateral, inhibition. When a Delta ligand belonging to one cell binds to the Notch receptor on a neighboring cell, the production of Delta ligands in the second cell is reduced. This amplifies any initial differences in the amount of Delta produced by each cell, and leads ultimately to them becoming distinct cell types. Now, Langen et al. show that this same mechanism is reactivated at a later stage of development during wiring up of the visual system. They used the fruit fly (Drosophila)—a model organism with a fully sequenced genome and short intergeneration time—to study a group of brain cells known as dorsal cluster neurons. At the end of the fruit fly larval stage, these neurons extend long axons across the brain to the opposite hemisphere: however, it is unclear how the neurons decide which cells to form connections with. Using genetically modified flies, Langen et al. showed that inhibiting Notch in a single dorsal cluster neuron caused that neuron to target a different cell: however, other neurons adjusted their choices accordingly so that the overall pattern of connections remained unchanged. Inhibiting Notch in a cluster of dorsal cluster neurons, on the other hand, disrupted the entire network, suggesting that Notch-mediated communication between neurons (via mutual inhibition) is needed to establish a robust wiring map. Langen et al. suggest that evolution has favored a mechanism that ensures that the overall pattern of connections within a circuit is preserved, while individual connections differ from one species member to the next.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2986294760