A multicellular rosette-mediated collective dendrite extension

  1. Li Fan
  2. Ismar Kovacevic
  3. Maxwell G Heiman
  4. Zhirong Bao  Is a corresponding author
  1. Sloan-Kettering Institute, United States
  2. Boston Children's Hospital, United States

Abstract

Coordination of neurite morphogenesis with surrounding tissues is crucial to the establishment of neural circuits, but the underlying cellular and molecular mechanisms remain poorly understood. We show that neurons in a C. elegans sensory organ, called the amphid, undergo a collective dendrite extension to form the sensory nerve. The amphid neurons first assemble into a multicellular rosette. The vertex of the rosette, which becomes the dendrite tips, is attached to the anteriorly migrating epidermis and carried to the sensory depression, extruding the dendrites away from the neuronal cell bodies. Multiple adhesion molecules including DYF-7, SAX-7, HMR-1 and DLG-1 function redundantly in rosette-to-epidermis attachment. PAR-6 is localized to the rosette vertex and dendrite tips, and promotes DYF-7 localization and dendrite extension. Our results suggest a collective mechanism of neurite extension that is distinct from the classical pioneer-follower model and highlight the role of mechanical cues from surrounding tissues in shaping neurites.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Li Fan

    Developmental Biology, Sloan-Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ismar Kovacevic

    Developmental Biology Program, Sloan-Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maxwell G Heiman

    Division of Genetics and Genomics, Boston Children's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2557-6490
  4. Zhirong Bao

    Developmental Biology Program, Sloan-Kettering Institute, New York, United States
    For correspondence
    baoz@mskcc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2201-2745

Funding

National Institutes of Health (R01 GM097576)

  • Zhirong Bao

National Institutes of Health (R24 OD016474)

  • Zhirong Bao

National Institutes of Health (R01 GM108754)

  • Maxwell G Heiman

The authors declare that the funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: May 3, 2018
  2. Accepted: February 14, 2019
  3. Accepted Manuscript published: February 15, 2019 (version 1)
  4. Version of Record published: March 5, 2019 (version 2)

Copyright

© 2019, Fan 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

  • 1,726
    Page views
  • 300
    Downloads
  • 19
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

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)

  1. Li Fan
  2. Ismar Kovacevic
  3. Maxwell G Heiman
  4. Zhirong Bao
(2019)
A multicellular rosette-mediated collective dendrite extension
eLife 8:e38065.
https://doi.org/10.7554/eLife.38065

Further reading

    1. Computational and Systems Biology
    2. Neuroscience
    Bo Shen, Kenway Louie, Paul W Glimcher
    Research Article

    Inhibition is crucial for brain function, regulating network activity by balancing excitation and implementing gain control. Recent evidence suggests that beyond simply inhibiting excitatory activity, inhibitory neurons can also shape circuit function through disinhibition. While disinhibitory circuit motifs have been implicated in cognitive processes including learning, attentional selection, and input gating, the role of disinhibition is largely unexplored in the study of decision-making. Here, we show that disinhibition provides a simple circuit motif for fast, dynamic control of network state and function. This dynamic control allows a disinhibition-based decision model to reproduce both value normalization and winner-take-all dynamics, the two central features of neurobiological decision-making captured in separate existing models with distinct circuit motifs. In addition, the disinhibition model exhibits flexible attractor dynamics consistent with different forms of persistent activity seen in working memory. Fitting the model to empirical data shows it captures well both the neurophysiological dynamics of value coding and psychometric choice behavior. Furthermore, the biological basis of disinhibition provides a simple mechanism for flexible top-down control of the network states, enabling the circuit to capture diverse task-dependent neural dynamics. These results suggest a biologically plausible unifying mechanism for decision-making and emphasize the importance of local disinhibition in neural processing.

    1. Medicine
    2. Neuroscience
    Gen Li, Binshi Bo ... Xiaojie Duan
    Research Article

    The available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-treated rats) and observed an immediate (within seconds to minutes) alleviation of depressive-like symptoms with a high-response rate. Simultaneous functional MRI (fMRI) conducted on the same sets of depressive rats used in behavioral tests revealed DBS-induced activation of multiple regions in afferent and efferent circuitry of the LHb. The activation levels of brain regions connected to the medial LHb (M-LHb) were correlated with the extent of behavioral improvements. Rats with more medial stimulation sites in the LHb exhibited greater antidepressant effects than those with more lateral stimulation sites. These results indicated that the antidromic activation of the limbic system and orthodromic activation of the monoaminergic systems connected to the M-LHb played a critical role in the rapid antidepressant effects of LHb-DBS. This study indicates that M-LHb-DBS might act as a valuable, rapid-acting antidepressant therapeutic strategy for treatment-resistant depression and demonstrates the potential of using fMRI activation of specific brain regions as biomarkers to predict and evaluate antidepressant efficacy.