Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire

Abstract

The architectures of dendritic trees are crucial for the wiring and function of neuronal circuits because they determine coverage of receptive territories, as well as the nature and strength of sensory or synaptic inputs. Here, we describe a cell-intrinsic pathway sculpting dendritic arborization (da) neurons in Drosophila that requires Longitudinals Lacking (Lola), a BTB/POZ transcription factor, and its control of the F-actin cytoskeleton through Spire (Spir), an actin nucleation protein. Loss of Lola from da neurons reduced the overall length of dendritic arbors, increased the expression of Spir, and produced inappropriate F-actin-rich dendrites at positions too near the cell soma. Selective removal of Lola from only class IV da neurons decreased the evasive responses of larvae to nociception. The increased Spir expression contributed to the abnormal F-actinrich dendrites and the decreased nocifensive responses because both were suppressed by reduced dose of Spir. Thus, an important role of Lola is to limit expression of Spir to appropriate levels within da neurons. We found Spir to be expressed in dendritic arbors and to be important for their development. Removal of Spir from class IV da neurons reduced F-actin levels and total branch number, shifted the position of greatest branch density away from the cell soma, and compromised nocifensive behavior. We conclude that the Lola-Spir pathway is crucial for the spatial arrangement of branches within dendritic trees and for neural circuit function because it provides balanced control of the F-actin cytoskeleton.

Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw

“…First, terminal branch distribution along the proximal-distal axis depends on microtubule-based processes; perturbing microtubule-based transport leads to a distal-proximal shift in the distribution of terminal dendrites in C4da arbors (Satoh et al, 2008;Zheng et al, 2008). Interestingly, modulating the activity of the F-actin nucleator Spire also affects terminal dendrite positioning along the proximal-distal axis (Ferreira et al, 2014), suggesting that multiple pathways contribute to the fidelity of branch placement. Second, terminal dendrites rely on dedicated programs that may act locally to regulate terminal dendrite patterning.…”

Broad‐complex, tramtrack, and bric‐à‐brac (BTB) proteins: Critical regulators of development

“…Mutation of lola results in increased spire expression, as well as decreased ISNb motor neuron innervation of ventrolateral musculature, and this phenotype was rescued by heterozygosity for spire (Gates et al, 2011;Madden et al, 1999). It has also been shown that Lola represses expression of spire in dendritic arborization neurons of the PNS, thereby limiting the formation of F-actin branches and controlling branch arrangement in dendritic arbors (Ferreira et al, 2014). The expression of most known Lola isoforms in projection neurons of the developing olfactory system and the requirement for Lola in dendrite and axon targeting in these neurons suggest that Lola is a key transcriptional regulator of the cytoskeleton during nervous system development (Spletter et al, 2007).…”

Transcription factors and effectors that regulate neuronal morphology

“…One shared upregulated target of Ab and Knot that emerged from this analysis was the BTB/POZ transcription factor Lola, and a subsequent study by van Meyel and colleagues demonstrated that Lola controls dendritic morphogenesis through the actin nucleating protein Spire (Ferreira et al, 2014). Lola is expressed in all classes of da neurons, where it is required for dendritic branching and growth.…”