Chronology-based architecture of descending circuits that underlie the development of locomotor repertoire after birth

  1. Avinash Pujala
  2. Minoru Koyama  Is a corresponding author
  1. Janelia Research Campus, Howard Hughes Medical Institute, United States

Abstract

The emergence of new and increasingly sophisticated behaviors after birth is accompanied by dramatic increase of newly established synaptic connections in the nervous system. Little is known, however, of how nascent connections are organized to support such new behaviors alongside existing ones. To understand this, in the larval zebrafish we examined the development of spinal pathways from hindbrain V2a neurons and the role of these pathways in the development of locomotion. We found that new projections are continually layered laterally to existing neuropil, and give rise to distinct pathways that function in parallel to existing pathways. Across these chronologically layered pathways, the connectivity patterns and biophysical properties vary systematically to support a behavioral repertoire with a wide range of kinematics and dynamics. Such layering of new parallel circuits equipped with systematically changing properties may be central to the postnatal diversification and increasing sophistication of an animal's behavioral repertoire.

Data availability

Source data files have been provided for numerical data that are represented as graphs in Figure 3C, 7D, 7E, 7F, 8E, 9J, 9K, 9L, and 10C.

Article and author information

Author details

  1. Avinash Pujala

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8758-1634
  2. Minoru Koyama

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    koyamam@janelia.hhmi.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9774-9223

Funding

Howard Hughes Medical Institute

  • Avinash Pujala
  • Minoru Koyama

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

Ethics

Animal experimentation: All experiments presented in this study were conducted in accordance with the animal research guidelines from the National Institutes of Health and were approved by the Institutional Animal Care and Use Committee and Institutional Biosafety Committee of Janelia Research Campus. (16-145).

Reviewing Editor

  1. Vatsala Thirumalai, National Centre for Biological Sciences, India

Publication history

  1. Received: September 20, 2018
  2. Accepted: February 22, 2019
  3. Accepted Manuscript published: February 25, 2019 (version 1)
  4. Version of Record published: April 4, 2019 (version 2)

Copyright

© 2019, Pujala & Koyama

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

  • 2,767
    Page views
  • 405
    Downloads
  • 24
    Citations

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

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. Avinash Pujala
  2. Minoru Koyama
(2019)
Chronology-based architecture of descending circuits that underlie the development of locomotor repertoire after birth
eLife 8:e42135.
https://doi.org/10.7554/eLife.42135
  1. Further reading

Further reading

    1. Developmental Biology
    Sol Sotillos, Isabel von der Decken ... James Castelli-Gair Hombría
    Research Article Updated

    The identification of genes affecting gonad development is essential to understand the mechanisms causing Variations/Differences in Sex Development (DSD). Recently, a DLC3 mutation was associated with male gonadal dysgenesis in 46,XY DSD patients. We have studied the requirement of Cv-c, the Drosophila ortholog of DLC3, in Drosophila gonad development, as well as the functional capacity of DLC3 human variants to rescue cv-c gonad defects. We show that Cv-c is required to maintain testis integrity during fly development. We find that Cv-c and human DLC3 can perform the same function in fly embryos, as flies carrying wild type but not patient DLC3 variations can rescue gonadal dysgenesis, suggesting functional conservation. We also demonstrate that the StART domain mediates Cv-c's function in the male gonad independently from the GAP domain's activity. This work demonstrates a role for DLC3/Cv-c in male gonadogenesis and highlights a novel StART domain mediated function required to organize the gonadal mesoderm and maintain its interaction with the germ cells during testis development.

    1. Cell Biology
    2. Developmental Biology
    Peng Ding, Chuan Gao ... Junjie Gao
    Research Article Updated

    The skeletal system contains a series of sophisticated cellular lineages arising from the mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) that determine the homeostasis of bone and bone marrow. Here, we reasoned that osteocyte may exert a function in regulation of these lineage cell specifications and tissue homeostasis. Using a mouse model of conditional deletion of osteocytes by the expression of diphtheria toxin subunit α in dentin matrix protein 1 (DMP1)-positive osteocytes, we demonstrated that partial ablation of DMP1-positive osteocytes caused severe sarcopenia, osteoporosis, and degenerative kyphosis, leading to shorter lifespan in these animals. Osteocytes reduction altered mesenchymal lineage commitment, resulting in impairment of osteogenesis and induction of osteoclastogensis. Single-cell RNA sequencing further revealed that hematopoietic lineage was mobilized toward myeloid lineage differentiation with expanded myeloid progenitors, neutrophils, and monocytes, while the lymphopoiesis was impaired with reduced B cells in the osteocyte ablation mice. The acquisition of a senescence-associated secretory phenotype (SASP) in both osteogenic and myeloid lineage cells was the underlying cause. Together, we showed that osteocytes play critical roles in regulation of lineage cell specifications in bone and bone marrow through mediation of senescence.