The laminar organization of the Drosophila ellipsoid body is semaphorin-dependent and prevents the formation of ectopic synaptic connections
Abstract
The ellipsoid body (EB) in the Drosophila brain is a central complex (CX) substructure that harbors circumferentially laminated ring (R) neuron axons and mediates multifaceted sensory integration and motor coordination functions. However, what regulates R axon lamination and how lamination affects R neuron function remain unknown. We show here that the EB is sequentially innervated by small-field and large-field neurons, and that early-developing EB neurons play an important regulatory role in EB laminae formation. The transmembrane proteins semaphorin-1a and plexin A function together to regulate R axon lamination. R neurons recruit both GABA and GABA-A receptors to their axon terminals in the EB, and optogenetic stimulation coupled with electrophysiological recordings show that Sema-1a–dependent R axon lamination is required for preventing the spread of synaptic inhibition between adjacent EB lamina. These results provide direct evidence that EB lamination is critical for local pre-synaptic inhibitory circuit organization.
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Xiaojun Xie
- Matthew P Brown
- Sarah P Mitchell
- Alex L Kolodkin
National Institutes of Health (1R01 NS079584)
- Masashi Tabuchi
- Mark N Wu
National Institutes of Health (1R21 NS088521)
- Masashi Tabuchi
- Mark N Wu
National Institutes of Health (P30 NS50274)
- Alex L Kolodkin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mani Ramaswami, Trinity College Dublin, Ireland
Version history
- Received: January 20, 2017
- Accepted: June 19, 2017
- Accepted Manuscript published: June 20, 2017 (version 1)
- Accepted Manuscript updated: June 21, 2017 (version 2)
- Version of Record published: July 14, 2017 (version 3)
Copyright
© 2017, Xie et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,226
- views
-
- 499
- downloads
-
- 37
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Computational and Systems Biology
- Developmental Biology
Organisms utilize gene regulatory networks (GRN) to make fate decisions, but the regulatory mechanisms of transcription factors (TF) in GRNs are exceedingly intricate. A longstanding question in this field is how these tangled interactions synergistically contribute to decision-making procedures. To comprehensively understand the role of regulatory logic in cell fate decisions, we constructed a logic-incorporated GRN model and examined its behavior under two distinct driving forces (noise-driven and signal-driven). Under the noise-driven mode, we distilled the relationship among fate bias, regulatory logic, and noise profile. Under the signal-driven mode, we bridged regulatory logic and progression-accuracy trade-off, and uncovered distinctive trajectories of reprogramming influenced by logic motifs. In differentiation, we characterized a special logic-dependent priming stage by the solution landscape. Finally, we applied our findings to decipher three biological instances: hematopoiesis, embryogenesis, and trans-differentiation. Orthogonal to the classical analysis of expression profile, we harnessed noise patterns to construct the GRN corresponding to fate transition. Our work presents a generalizable framework for top-down fate-decision studies and a practical approach to the taxonomy of cell fate decisions.
-
- Developmental Biology
- Evolutionary Biology
Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the MIR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked MIR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the MIR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.