Academic Journal
Whole-neuron morphology and genetic identity define cell types and reveal principles of brain-wide connectivity.
| Title: | Whole-neuron morphology and genetic identity define cell types and reveal principles of brain-wide connectivity. |
|---|---|
| Authors: | Wang Y; Allen Institute for Brain Science, Seattle, WA, USA; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China. Electronic address: wangy62@gmail.com., Kuo HC; Allen Institute for Brain Science, Seattle, WA, USA., Kuang X; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China; Oujiang Laboratory, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China., Yao S; Allen Institute for Brain Science, Seattle, WA, USA., Lesnar P; Allen Institute for Brain Science, Seattle, WA, USA., Ng L; Allen Institute for Brain Science, Seattle, WA, USA., Li Y; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China., El-Hifnawi L; Allen Institute for Brain Science, Seattle, WA, USA., Chen N; Allen Institute for Brain Science, Seattle, WA, USA., Zhang K; Allen Institute for Brain Science, Seattle, WA, USA., Li EM; Georgia Institute of Technology, Atlanta, GA, USA., Ben-Simon Y; Allen Institute for Brain Science, Seattle, WA, USA., Ding SL; Allen Institute for Brain Science, Seattle, WA, USA., Wang Q; Allen Institute for Brain Science, Seattle, WA, USA., Karlsson T; Allen Institute for Brain Science, Seattle, WA, USA., Dalley R; Allen Institute for Brain Science, Seattle, WA, USA., Williams G; Allen Institute for Brain Science, Seattle, WA, USA., Xiong W; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China., Chen C; Oujiang Laboratory, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China., Chen K; Oujiang Laboratory, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China., Huang Z; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China., Yu ZF; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China., Xu WJ; Allen Institute for Brain Science, Seattle, WA, USA., Ahmadinia L; Allen Institute for Brain Science, Seattle, WA, USA., Walling-Bell S; Allen Institute for Brain Science, Seattle, WA, USA., Andrade J; Allen Institute for Brain Science, Seattle, WA, USA., Gliko O; Allen Institute for Brain Science, Seattle, WA, USA., Mallory M; Allen Institute for Brain Science, Seattle, WA, USA., Farrel C; Allen Institute for Brain Science, Seattle, WA, USA., Sutton B; Allen Institute for Brain Science, Seattle, WA, USA., Jin K; Allen Institute for Brain Science, Seattle, WA, USA., Yao Z; Allen Institute for Brain Science, Seattle, WA, USA., Halterman C; Allen Institute for Brain Science, Seattle, WA, USA., Ronellenfitch K; Allen Institute for Brain Science, Seattle, WA, USA., Esposito L; Allen Institute for Brain Science, Seattle, WA, USA., Sunkin S; Allen Institute for Brain Science, Seattle, WA, USA., Kruse L; Allen Institute for Brain Science, Seattle, WA, USA., Luo Q; HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou, China; State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Sanya, China., Gong H; HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou, China., Li A; HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou, China., Li X; HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou, China; State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Sanya, China., Qu J; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China; Oujiang Laboratory, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China., Choi H; Georgia Institute of Technology, Atlanta, GA, USA., Mihalas S; Allen Institute for Brain Science, Seattle, WA, USA., Zhuang J; Allen Institute for Brain Science, Seattle, WA, USA., Sorensen S; Allen Institute for Brain Science, Seattle, WA, USA. |
| Source: | Cell reports [Cell Rep] 2026 Jun 23; Vol. 45 (6), pp. 117469. Date of Electronic Publication: 2026 Jun 16. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| MeSH Terms: | Neurons*/cytology , Neurons*/metabolism , Brain*/cytology , Brain*/physiology, Axons/metabolism ; Animals ; Mice ; Connectome |
| Abstract: | Neocortex contains diverse excitatory neurons whose dendritic and axonal architectures shape computation and long-range communication, yet a unified framework linking neuronal structure, molecular identity, and brain-wide connectivity is lacking. Here, we combine complete whole-neuron morphology (WNM) reconstructions with paired genetic identities across 15 mouse cortical areas to define organizing principles of cortical wiring at single-cell resolution. We identify 10 stable excitatory cell types with conserved morphology and predominant genetic correspondence. Their full axonal target spectra reveal four output architectures and cell-type-resolved principles of corticocortical and cortico-subcortical organization, including modular convergence in downstream targets, distinct spatial topographical rules across corticocortical and corticofugal pathways, and hierarchical organization better predicted by targeting probability and projection distribution than projection strength, while refining bulk-derived projectomes by resolving artifacts from bulk approaches. Together, these findings establish WNM as a principled axis for defining cortical cell types as building blocks of large-scale connectomes. (Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests There are no competing interests. |
| Contributed Indexing: | Keywords: CP: Neuroscience; cell-type-resolved connectomics; convergence motifs; cortical excitatory cell types; corticocortical and cortico-subcortical projectomes; corticofugal pathways; genetic identity; hierarchical organization; single-cell resolution; topographic organization; whole-neuron morphology |
| Entry Date(s): | Date Created: 20260616 Date Completed: 20260625 Latest Revision: 20260625 |
| Update Code: | 20260625 |
| DOI: | 10.1016/j.celrep.2026.117469 |
| PMID: | 42301808 |
| Database: | MEDLINE |
| ISSN: | 2211-1247 |
|---|---|
| DOI: | 10.1016/j.celrep.2026.117469 |