Neocortical pyramidal neurons with axons emerging from dendrites are frequent in non-primates, but rare in monkey and human

  1. Petra Wahle  Is a corresponding author
  2. Eric Sobierajski
  3. Ina Gasterstädt
  4. Nadja Lehmann
  5. Susanna Weber
  6. Joachim HR Lübke
  7. Maren Engelhardt
  8. Claudia Distler
  9. Gundela Meyer
  1. Ruhr University Bochum, Germany
  2. Heidelberg University, Germany
  3. Research Centre Jülich GmbH, Germany
  4. Johannes Kepler University, Austria
  5. University of La Laguna, Spain

Abstract

The canonical view of neuronal function is that inputs are received by dendrites and somata, become integrated in the somatodendritic compartment and upon reaching a sufficient threshold, generate axonal output with axons emerging from the cell body. The latter is not necessarily the case. Instead, axons may originate from dendrites. The terms 'axon carrying dendrite' (AcD) and 'AcD neurons' have been coined to describe this feature. In rodent hippocampus, AcD cells are shown to be functionally 'privileged', since inputs here can circumvent somatic integration and lead to immediate action potential initiation in the axon. Here, we report on the diversity of axon origins in neocortical pyramidal cells of rodent, ungulate, carnivore, and primate. Detection methods were Thy-1-EGFP labeling in mouse, retrograde biocytin tracing in rat, cat, ferret, and macaque, SMI-32/βIV-spectrin immunofluorescence in pig, cat, and macaque, and Golgi staining in macaque and human. We found that in non-primate mammals, 10-21% of pyramidal cells of layers II-VI had an AcD. In marked contrast, in macaque and human, this proportion was lower, and was particularly low for supragranular neurons. A comparison of six cortical areas (sensory, association, limbic) in three macaques yielded percentages of AcD cells which varied by a factor of 2 between the areas and between the individuals. Unexpectedly, pyramidal cells in the white matter of postnatal cat and aged human cortex exhibit AcDs to much higher percentages. In addition, interneurons assessed in developing cat and adult human cortex had AcDs at type-specific proportions and for some types at much higher percentages than pyramidal cells. Our findings expand the current knowledge regarding the distribution and proportion of AcD cells in neocortex of non-primate taxa, which strikingly differ from primates where these cells are mainly found in deeper layers and white matter.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 3 , 4, 5, 6, 7

Article and author information

Author details

  1. Petra Wahle

    Developmental Neurobiology, Ruhr University Bochum, Bochum, Germany
    For correspondence
    petra.wahle@rub.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8710-0375
  2. Eric Sobierajski

    Developmental Neurobiology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Ina Gasterstädt

    Developmental Neurobiology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Nadja Lehmann

    Mannheim Center for Translational Neuroscience, Heidelberg University, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4801-3057
  5. Susanna Weber

    Mannheim Center for Translational Neuroscience, Heidelberg University, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Joachim HR Lübke

    Research Centre Jülich GmbH, Jülich, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4086-3199
  7. Maren Engelhardt

    Faculty of Medicine, Johannes Kepler University, Linz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  8. Claudia Distler

    Faculty of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Gundela Meyer

    Department of Basic Medical Science, University of La Laguna, Santa Cruz de Tenerife, Spain
    Competing interests
    The authors declare that no competing interests exist.

Funding

Deutsche Forschungsgemeinschaft (WA 541/13-1)

  • Petra Wahle

Deutsche Forschungsgemeinschaft (WA 541/15-1)

  • Petra Wahle

Deutsche Forschungsgemeinschaft (EN 1240/2-1)

  • Maren Engelhardt

Deutsche Forschungsgemeinschaft (Ho-450/25-1)

  • Claudia Distler

Deutsche Forschungsgemeinschaft (SFB 509/A11)

  • Claudia Distler

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

Reviewing Editor

  1. Kristine Krug, Otto-von-Guericke University Magdeburg, Germany

Ethics

Human subjects: The data presented in this paper were collected via tissue sharing and from material that had originally been processed for projects not related to the present topic, i.e. no animals were sacrificed specifically for the present study. Human material was provided by Prof. Meyer and Prof. Lübke from previously published studies.

Version history

  1. Received: December 3, 2021
  2. Preprint posted: December 27, 2021 (view preprint)
  3. Accepted: April 19, 2022
  4. Accepted Manuscript published: April 20, 2022 (version 1)
  5. Version of Record published: June 1, 2022 (version 2)

Copyright

© 2022, Wahle 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

  • 3,213
    Page views
  • 767
    Downloads
  • 10
    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. Petra Wahle
  2. Eric Sobierajski
  3. Ina Gasterstädt
  4. Nadja Lehmann
  5. Susanna Weber
  6. Joachim HR Lübke
  7. Maren Engelhardt
  8. Claudia Distler
  9. Gundela Meyer
(2022)
Neocortical pyramidal neurons with axons emerging from dendrites are frequent in non-primates, but rare in monkey and human
eLife 11:e76101.
https://doi.org/10.7554/eLife.76101

Share this article

https://doi.org/10.7554/eLife.76101

Further reading

    1. Evolutionary Biology
    Alexei V Tkachenko, Sergei Maslov
    Research Article

    Life as we know it relies on the interplay between catalytic activity and information processing carried out by biological polymers. Here we present a plausible pathway by which a pool of prebiotic information-coding oligomers could acquire an early catalytic function, namely sequence-specific cleavage activity. Starting with a system capable of non-enzymatic templated replication, we demonstrate that even non-catalyzed spontaneous cleavage would promote proliferation by generating short fragments that act as primers. Furthermore, we show that catalytic cleavage function can naturally emerge and proliferate in this system. Specifically, a cooperative catalytic network with four subpopulations of oligomers is selected by the evolution in competition with chains lacking catalytic activity. The cooperative system emerges through the functional differentiation of oligomers into catalysts and their substrates. The model is inspired by the structure of the hammerhead RNA enzyme as well as other DNA- and RNA-based enzymes with cleavage activity that readily emerge through natural or artificial selection. We identify the conditions necessary for the emergence of the cooperative catalytic network. In particular, we show that it requires the catalytic rate enhancement over the spontaneous cleavage rate to be at least 102–103, a factor consistent with the existing experiments. The evolutionary pressure leads to a further increase in catalytic efficiency. The presented mechanism provides an escape route from a relatively simple pairwise replication of oligomers toward a more complex behavior involving catalytic function. This provides a bridge between the information-first origin of life scenarios and the paradigm of autocatalytic sets and hypercycles, albeit based on cleavage rather than synthesis of reactants.

    1. Cell Biology
    2. Evolutionary Biology
    Jonathan E Phillips, Duojia Pan
    Research Advance

    The genomes of close unicellular relatives of animals encode orthologs of many genes that regulate animal development. However, little is known about the function of such genes in unicellular organisms or the evolutionary process by which these genes came to function in multicellular development. The Hippo pathway, which regulates cell proliferation and tissue size in animals, is present in some of the closest unicellular relatives of animals, including the amoeboid organism Capsaspora owczarzaki. We previously showed that the Capsaspora ortholog of the Hippo pathway nuclear effector Yorkie/YAP/TAZ (coYki) regulates actin dynamics and the three-dimensional morphology of Capsaspora cell aggregates, but is dispensable for cell proliferation control (Phillips et al., 2022). However, the function of upstream Hippo pathway components, and whether and how they regulate coYki in Capsaspora, remained unknown. Here, we analyze the function of the upstream Hippo pathway kinases coHpo and coWts in Capsaspora by generating mutant lines for each gene. Loss of either kinase results in increased nuclear localization of coYki, indicating an ancient, premetazoan origin of this Hippo pathway regulatory mechanism. Strikingly, we find that loss of either kinase causes a contractile cell behavior and increased density of cell packing within Capsaspora aggregates. We further show that this increased cell density is not due to differences in proliferation, but rather actomyosin-dependent changes in the multicellular architecture of aggregates. Given its well-established role in cell density-regulated proliferation in animals, the increased density of cell packing in coHpo and coWts mutants suggests a shared and possibly ancient and conserved function of the Hippo pathway in cell density control. Together, these results implicate cytoskeletal regulation but not proliferation as an ancestral function of the Hippo pathway kinase cascade and uncover a novel role for Hippo signaling in regulating cell density in a proliferation-independent manner.