---
title: "Excitatory progenitor diversification in the rhombic lip drives evolution of new cerebellar nuclei"
id: "biorxiv-18-evolution-of-new-cerebellar-nuclei-by-excitatory-progenitor-diversification-in"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-18-evolution-of-new-cerebellar-nuclei-by-excitatory-progenitor-diversification-in"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.17.751883v1?rss=1"
published_at: "2026-09-20T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Excitatory progenitor diversification in the rhombic lip drives evolution of new cerebellar nuclei
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-18-evolution-of-new-cerebellar-nuclei-by-excitatory-progenitor-diversification-in
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.17.751883v1?rss=1)
- **Published At:** 2026-09-20T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study uses developmental **single-cell** and **spatial transcriptomics** time courses in mouse and chicken to investigate how cerebellar nuclei diversify during development and evolution. - New cerebellar nuclei arise through production of excitatory neurons from **nucleus-specific progenitors** located in the early and late **rhombic lip (RL)**. - Inhibitory neurons do not originate from these nucleus-specific progenitors; instead, they incorporate into nuclear territories after excitatory nuclei are established. - Diversification of the **early RL** generates evolutionarily newer, canonical cerebellar nuclei that underlie increasingly higher-order functions. - Nuclear identity and spatial organization are established in part by the **co-option of border formation programs** within conserved progenitor cell types, according to the authors' analyses. - The **late RL** produces higher-order subnuclei of the medial nucleus and forms a non-canonical olivocerebellar circuit distinct from canonical patterning. - The results support a model where new brain regions evolve primarily through developmental diversification of **excitatory progenitors** accompanied by spatial segregation of conserved sister cell types, with generic inhibitory neurons added subsequently. - Work was performed in mouse and chicken models; the authors present comparative developmental evidence rather than direct evolutionary genetic experiments. - The article is a preprint and has not undergone peer review; no competing interests were declared by the authors.
## Clinical Analysis & Structured Key Points
Evolution of new cerebellar nuclei by excitatory progenitor diversification in the early rhombic lip | bioRxiv Skip to main content New Results Evolution of new cerebellar nuclei by excitatory progenitor diversification in the early rhombic lip View ORCID Profile Manjari M-G Anant , Eli Clemens Zuercher , Maggie Lowman , Caleb Shi , Dylan Z. Faltine-Gonzalez , View ORCID Profile Michael L. Piacentino , View ORCID Profile Jean Fan , View ORCID Profile Justus M. Kebschull doi: https://doi.org/10.64898/2026.09.17.751883 Manjari M-G Anant 1 Johns Hopkins University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Manjari M-G Anant Eli Clemens Zuercher 1 Johns Hopkins University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Maggie Lowman 1 Johns Hopkins University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Caleb Shi 1 Johns Hopkins University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Dylan Z. Faltine-Gonzalez 1 Johns Hopkins University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Michael L. Piacentino 2 Johns Hopkins University School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Michael L. Piacentino Jean Fan 1 Johns Hopkins University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jean Fan Justus M. Kebschull 1 Johns Hopkins University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Justus M. Kebschull For correspondence: kebschull{at}jhu.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract The cerebellar nuclei, the output regions of the cerebellum, have evolved via repeated duplication of a conserved cell type set to produce different numbers of nuclei across species. Here, we investigate the mechanism underlying this process using developmental single-cell and spatial transcriptomics time courses in mouse and chicken. We show that new nuclei formation is governed by excitatory neurons born from nucleus-specific progenitors in the early and late rhombic lip (RL), with inhibitory neurons incorporating into established nuclear territories. Evolutionarily newer canonical cerebellar nuclei with increasingly higher-order functions are produced by diversification of the early RL, where nuclear identity and spatial organization are established in part by co-option of border formation programs in conserved progenitor cell types. In contrast, the late RL generates the higher-order subnuclei of the medial nucleus and forms a non-canonical olivocerebellar circuit. Together, our findings suggest that new brain regions can evolve through developmental diversification of excitatory progenitors and spatial segregation of conserved sister cell types with generic inhibitory neurons filling in after. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared David and Lucile Packard Foundation, https://ror.org/032atxq54 Esther A. & Joseph Klingenstein Fund, https://ror.org/01q222b25 Alfred P. Sloan Foundation, https://ror.org/052csg198 Pershing Square Foundation, https://ror.org/04tce9s05 National Institutes of Health, https://ror.org/01cwqze88 , R35GM142889 National Institutes of Health, https://ror.org/01cwqze88 , R35GM155257 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . Back to top Previous Next Posted September 20, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Evolution of new cerebellar nuclei by excitatory progenitor diversification in the early rhombic lip Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Evolution of new cerebellar nuclei by excitatory progenitor diversification in the early rhombic lip Manjari M-G Anant , Eli Clemens Zuercher , Maggie Lowman , Caleb Shi , Dylan Z. Faltine-Gonzalez , Michael L. Piacentino , Jean Fan , Justus M. Kebschull bioRxiv 2026.09.17.751883; doi: https://doi.org/10.64898/2026.09.17.751883 Share This Article: Copy Citation Tools Evolution of new cerebellar nuclei by excitatory progenitor diversification in the early rhombic lip Manjari M-G Anant , Eli Clemens Zuercher , Maggie Lowman , Caleb Shi , Dylan Z. Faltine-Gonzalez , Michael L. Piacentino , Jean Fan , Justus M. Kebschull bioRxiv 2026.09.17.751883; doi: https://doi.org/10.64898/2026.09.17.751883 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Neuroscience Subject Areas All Articles Animal Behavior and Cognition (8013) Biochemistry (18739) Bioengineering (14888) Bioinformatics (44418) Biophysics (22599) Cancer Biology (19723) Cell Biology (26899) Clinical Trials (138) Developmental Biology (13965) Ecology (21005) Epidemiology (2067) Evolutionary Biology (25455) Genetics (16166) Genomics (23507) Immunology (18705) Microbiology (42503) Molecular Biology (18059) Neuroscience (93451) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5095) Physiology (8114) Plant Biology (15999) Scientific Communication and Education (2095) Synthetic Biology (4560) Systems Biology (10235) Zoology (2391)
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