Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex
- University of California, San Francisco, United States
- Baylor College of Medicine, United States
- University of Tübingen, Germany
- Karolinska Institutet, Sweden
Abstract
Clones of excitatory neurons derived from a common progenitor have been proposed to serve as elementary information processing modules in the neocortex. To characterize the cell types and circuit diagram of clonally related neurons, we performed multi-cell patch clamp recordings and Patch-seq on neurons derived from Nestin-positive progenitors labeled by tamoxifen induction at embryonic day 10.5. The resulting clones are derived from two radial glia on average, span cortical layers 2-6, and are composed of a random sampling of transcriptomic cell types. We find an interaction between shared lineage and connectivity: related neurons are more likely to be connected vertically across cortical layers, but not laterally within the same layer. These findings challenge the view that related neurons show uniformly increased connectivity and suggest that integration of vertical intra-clonal input with lateral inter-clonal input may represent a developmentally programmed connectivity motif supporting the emergence of functional circuits.
Data availability
Sequencing data have been deposited in GEO under accession code GSE140946. All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3 and 4. The source data provided for Figure 4 also apply to Figure 5 and Table 1.
-
Cell type composition and circuit organization of neocortical radial clonesNCBI Gene Expression Omnibus, GSE140946.
Article and author information
Author details
Kimberley F Tolias
Andreas Savas Tolias
Funding
Baylor College of Medicine (Optical Imaging and Vital Microscopy Core)
- Andreas Savas Tolias
Baylor College of Medicine (Faculty start-up fund)
- Xiaolong Jiang
National Institutes of Health (F30MH095440,T32GM007330)
- Cathryn R Cadwell
National Institutes of Health (F30MH112312)
- Paul G Fahey
Baylor Research Advocates for Student Scientists (BRASS Scholar Award)
- Cathryn R Cadwell
- Paul G Fahey
National Institutes of Health (R01MH103108,R01DA028525,DP1EY023176,P30EY002520,T32EY07001,DP1OD008301)
- Andreas Savas Tolias
National Science Foundation (707359)
- Andreas Savas Tolias
Svenska Forskningsrådet Formas
- Rickard Sandberg
Vallee Foundation
- Rickard Sandberg
Deutsche Forschungsgemeinschaft (EXC 2064,BE5601/4-1)
- Philipp Berens
Bundesministerium für Bildung und Forschung (FKZ 01GQ1601)
- Philipp Berens
McKnight Foundation (McKnight Scholar Award)
- Andreas Savas Tolias
Arnold and Mabel Beckman Foundation (Young Investigator Award)
- Andreas Savas Tolias
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to an approved institutional animal care and use committee (IACUC) protocol of Baylor College of Medicine (protocol # AN-4703). Every effort was made to minimize suffering.
Reviewing Editor
- Anne E West, Duke University School of Medicine, United States
Version history
- Received: October 22, 2019
- Accepted: March 2, 2020
- Accepted Manuscript published: March 5, 2020 (version 1)
- Accepted Manuscript updated: March 6, 2020 (version 2)
- Version of Record published: April 16, 2020 (version 3)
Copyright
© 2020, Cadwell 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
-
- 3,787
- Page views
-
- 595
- Downloads
-
- 21
- 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)
Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex
eLife 9:e52951.
https://doi.org/10.7554/eLife.52951
Further reading
-
- Developmental Biology
- Neuroscience
Development of the nervous system depends on signaling centers – specialized cellular populations that produce secreted molecules to regulate neurogenesis in the neighboring neuroepithelium. In some cases, signaling center cells also differentiate to produce key types of neurons. The formation of a signaling center involves its induction, the maintenance of expression of its secreted molecules, and cell differentiation and migration events. How these distinct processes are coordinated during signaling center development remains unknown. By performing studies in mice, we show that Lmx1a acts as a master regulator to orchestrate the formation and function of the cortical hem (CH), a critical signaling center that controls hippocampus development. Lmx1a co-regulates CH induction, its Wnt signaling, and the differentiation and migration of CH-derived Cajal–Retzius neurons. Combining RNAseq, genetic, and rescue experiments, we identified major downstream genes that mediate distinct Lmx1a-dependent processes. Our work revealed that signaling centers in the mammalian brain employ master regulatory genes and established a framework for analyzing signaling center development.
-
- Developmental Biology
- Evolutionary Biology
Cephalochordates and tunicates represent the only two groups of invertebrate chordates, and extant cephalochordates – commonly known as amphioxus or lancelets – are considered the best proxy for the chordate ancestor, from which they split around 520 million years ago. Amphioxus has been an important organism in the fields of zoology and embryology since the 18th century, and the morphological and genomic simplicity of cephalochordates (compared to vertebrates) makes amphioxus an attractive model for studying chordate biology at the cellular and molecular levels. Here we describe the life cycle of amphioxus, and discuss the natural histories and habitats of the different species of amphioxus. We also describe their use as laboratory animal models, and discuss the techniques that have been developed to study different aspects of amphioxus.
