Cell-type homologies and the origins of the neocortex
Open accessAbstract
The six-layered neocortex is a uniquely mammalian structure with evolutionary origins that remain in dispute. One long-standing hypothesis, based on similarities in neuronal connectivity, proposes that homologs of the layer 4 input and layer 5 output neurons of neocortex are present in the avian forebrain, where they contribute to specific nuclei rather than to layers. We devised a molecular test of this hypothesis based on layer-specific gene expression that is shared across rodent and carnivore neocortex. Our findings establish that the layer 4 input and the layer 5 output cell types are conserved across the amniotes, but are organized into very different architectures, forming nuclei in birds, cortical areas in reptiles, and cortical layers in mammals.
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In the three animal groups these brain regions have comparable gene-expression patterns (by EAG2, RORB, ER81, PCP4), as well as comparable afferent and efferent connections.
“in the three animal groups these brain regions have comparable gene-expression patterns (by EAG2, RORB, ER81, PCP4), as well as comparable afferent and efferent connections”
From The evolutionary and genetic origins of consciousness in the Cambrian Period over 500 million years ago (2013) · cites this paper as Dugas-Ford et al., 2012
The Results (Fig. 2 and the turtle-cortex passages; page unavailable) report comparable input/output cell-type markers in mammals, birds, and turtles, including EAG2, RORB, and ER81, and describe corresponding thalamic inputs. They also describe brainstem-directed outputs in mammals and birds. The copy does not establish comparable efferent connections in turtles, and PCP4 expression is reported for mammals and birds but not turtles. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe new studies revealed a nearly identical internal microcircuitry in birds and mammals.
“the new studies revealed a nearly identical internal microcircuitry in birds and mammals.”
From The evolutionary and genetic origins of consciousness in the Cambrian Period over 500 million years ago (2013) · cites this paper as Dugas-Ford et al., 2012
The Results describe a shared core circuit of sensory input and brainstem-directed output neurons, and the Discussion reports corresponding connectional and molecular cell-type properties in birds and mammals. But the Discussion emphasizes substantial differences in how those neurons are arranged—layers in mammals versus nuclei in birds—so the paper does not establish that their internal microcircuitry is nearly identical. (LLM, conf=0.88)
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Cites
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“In birds, similarly, conscious functions are being identified in their cerebral-cortex homologues, the Wulst and the dorsal ventricular ridge (DVR) (Rose et al., 2009; Dugas-Ford et al., 2012; Karten, 2013).”
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- Authors
- Dugas-Ford, J., Rowell, J. J., & Ragsdale, C. W.
- Affiliations
- Department of Neurobiology and Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637
- University of Chicago (US)
- ORCID
- Ragsdale, Clifton W.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-10
- Volume
- 109
- Issue
- 42
- Pages
- 16974-16979
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3479531
- OpenAlex
- W2022105630
- Cited by
- 278
- References
- 4
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 12 · 2023: 11 · 2022: 8 · 2021: 26 · 2020: 25 · 2019: 22 · 2018: 20 · 2017: 31 · 2016: 25 · 2015: 29 · 2014: 26 · 2013: 25 · 2012: 1
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- neocortex evolution, avian forebrain, neuronal connectivity
- MeSH terms
- Animals, Base Sequence, Birds, Biological Evolution, Image Processing, Computer-Assisted, Mammals, Microscopy, Fluorescence, Molecular Sequence Data, Phylogeny, Reptiles, Polymerase Chain Reaction, In Situ Hybridization, Fluorescence, Sequence Analysis, DNA, DNA Primers, DNA, Complementary, Neocortex
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