---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21948'
abstract:
- lang: eng
  text: The cerebral cortex comprises diverse neuron and glial cell types generated
    by radial glial progenitors (RGPs) during development. Although RGPs broadly differentiate
    according to temporally and spatially regulated molecular logics, the lineage
    hierarchies linking individual progenitors to defined cell (sub)types are not
    well understood. Clone-resolved transcriptomics, combining molecular barcoding
    and single-cell RNA sequencing, allow high-resolution lineage tracing at the single-clone/cell
    level across different species and models. In this mini-review, we synthesize
    recent advances in this field, uncovering unexpected lineage relationships in
    the developing brain, with a particular focus on the cerebral cortex. We further
    highlight new insights into species-specific differences in the developmental
    programs generating cell-type diversity, linking changes in clonal architecture
    to lineage diversification during cortical evolution.
acknowledgement: We wish to thank all members of the Hippenmeyer laboratory at ISTA
  for exciting discussions on the subject of this review. We apologize to colleagues
  whose work we could not cite and/or discuss in the frame of the available space.
  Work in the Hippenmeyer laboratory on the discussed topic is supported by ISTA institutional
  funds, an EMBO LTF (ALTF 994–2023) to F.P., FWF SFB F78 (10.55776/F78) to S.H.,
  and FWF Cluster of Excellence COE16 (10.55776/COE16) to S.H.
article_number: '102487'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Irene
  full_name: Varela Martínez, Irene
  id: a69b5985-8829-11f0-8fc2-d0af58f64471
  last_name: Varela Martínez
- first_name: Fabrizia
  full_name: Pipicelli, Fabrizia
  id: 649134fd-d012-11ed-8f82-db1e5050f9ba
  last_name: Pipicelli
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: 'Varela Martínez I, Pipicelli F, Hippenmeyer S. Tracing cell lineages in the
    developing brain: Insights from mosaic analysis and clone-resolved transcriptomics.
    <i>Current Opinion in Genetics &#38; Development</i>. 2026;99. doi:<a href="https://doi.org/10.1016/j.gde.2026.102487">10.1016/j.gde.2026.102487</a>'
  apa: 'Varela Martínez, I., Pipicelli, F., &#38; Hippenmeyer, S. (2026). Tracing
    cell lineages in the developing brain: Insights from mosaic analysis and clone-resolved
    transcriptomics. <i>Current Opinion in Genetics &#38; Development</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.gde.2026.102487">https://doi.org/10.1016/j.gde.2026.102487</a>'
  chicago: 'Varela Martínez, Irene, Fabrizia Pipicelli, and Simon Hippenmeyer. “Tracing
    Cell Lineages in the Developing Brain: Insights from Mosaic Analysis and Clone-Resolved
    Transcriptomics.” <i>Current Opinion in Genetics &#38; Development</i>. Elsevier,
    2026. <a href="https://doi.org/10.1016/j.gde.2026.102487">https://doi.org/10.1016/j.gde.2026.102487</a>.'
  ieee: 'I. Varela Martínez, F. Pipicelli, and S. Hippenmeyer, “Tracing cell lineages
    in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics,”
    <i>Current Opinion in Genetics &#38; Development</i>, vol. 99. Elsevier, 2026.'
  ista: 'Varela Martínez I, Pipicelli F, Hippenmeyer S. 2026. Tracing cell lineages
    in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics.
    Current Opinion in Genetics &#38; Development. 99, 102487.'
  mla: 'Varela Martínez, Irene, et al. “Tracing Cell Lineages in the Developing Brain:
    Insights from Mosaic Analysis and Clone-Resolved Transcriptomics.” <i>Current
    Opinion in Genetics &#38; Development</i>, vol. 99, 102487, Elsevier, 2026, doi:<a
    href="https://doi.org/10.1016/j.gde.2026.102487">10.1016/j.gde.2026.102487</a>.'
  short: I. Varela Martínez, F. Pipicelli, S. Hippenmeyer, Current Opinion in Genetics
    &#38; Development 99 (2026).
corr_author: '1'
date_created: 2026-06-07T22:01:35Z
date_published: 2026-05-29T00:00:00Z
date_updated: 2026-08-12T09:56:19Z
day: '29'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.gde.2026.102487
external_id:
  pmid:
  - '42214837'
has_accepted_license: '1'
intvolume: '        99'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.gde.2026.102487
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 7c084566-9f16-11ee-852c-c88a1dbbf1cf
  grant_number: ALTF 994-2023
  name: Role of cell lineage in generating cell-type diversity in developing neocortex’
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
  grant_number: F7805
  name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
    Mechanisms of Neural Stem Cell Lineage Progression
publication: Current Opinion in Genetics & Development
publication_identifier:
  eissn:
  - 1879-0380
  issn:
  - 0959-437X
publication_status: epub_ahead
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Tracing cell lineages in the developing brain: Insights from mosaic analysis
  and clone-resolved transcriptomics'
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 99
year: '2026'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22714'
abstract:
- lang: eng
  text: Radial glial progenitors (RGPs) generate all projection neurons (PNs) in the
    cerebral cortex through incompletely understood processes. We combined Mosaic
    Analysis with Double Markers at embryonic stages (E)12.5 and E13.5 with early
    postnatal callosal tracing to dissect RGP lineage progression. We find that multipotent
    RGPs generate all extra-telencephalic (ET) and intra-telencephalic (IT) PNs via
    parallel sublineages that emerge simultaneously at neurogenesis onset. ET-PN production
    progresses exclusively via small, self-consuming lineages; IT-PN lineages feature
    RGPs generating large translaminar outputs. The early emergence of IT-PN–fated
    RGPs, coinciding with a switch to direct neurogenesis, contributes to the stereotyped
    population-level progression of the multipotent lineage. We also identify POU3F
    transcription factors as candidate regulators of IT-PN fate via noncanonical mitotic
    chromatin binding. The results support a model whereby IT- and ET-PNs arise from
    an early bifurcation and parallel specification within the multipotent RGP lineage.
acknowledgement: 'We thank M. caouyette for the plasmid construction for Pou3f1overexpression;
  d. Pinto-Benito for valuable assistance with shRnA validation in n2A cells andqPcR
  experiments; c. Varela-Martínez for help with the code for graphical analysis; allmembers
  from the nieto’s lab for comment on the manuscript, specially to F. Martín for theinsightful
  discussions; J. c. Oliveros and J. A. García from the computational service of the
  cnBfor help with the analysis of RnAseq dataset; c. O. Sorzano for help with statistical
  analysis; andA. Oña and the service of Advance Optical Microscopy of the cnB for
  technical advice.Funding: i.V.-M. holds a fellowship funded by MciciU (PRe-2018-083376)
  and 2023 eMBOscientific exchange grant 10214. the work was funded by grants to M.n.
  (Pid2020-112831GB- i00 and Pid2023-146322nB- i00 by Mcin/Aei/10.13039/501100011033
  and by“eRdF A way of making europe”).'
article_processing_charge: Yes
article_type: original
author:
- first_name: Irene
  full_name: Varela Martínez, Irene
  id: a69b5985-8829-11f0-8fc2-d0af58f64471
  last_name: Varela Martínez
- first_name: Ana
  full_name: Villalba Requena, Ana
  id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
  last_name: Villalba Requena
  orcid: 0000-0002-5615-5277
- first_name: Jorge
  full_name: García-Marqués, Jorge
  last_name: García-Marqués
- first_name: Alfonso
  full_name: Aguilera, Alfonso
  last_name: Aguilera
- first_name: Diogo S.
  full_name: Castro, Diogo S.
  last_name: Castro
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
- first_name: Marta
  full_name: Nieto, Marta
  last_name: Nieto
citation:
  ama: Varela Martínez I, Villalba Requena A, García-Marqués J, et al. Early fate
    diversification of radial glial progenitors during corticogenesis. <i>Science
    Advances</i>. 2026;12(32):eadw5487. doi:<a href="https://doi.org/10.1126/sciadv.adw5487">10.1126/sciadv.adw5487</a>
  apa: Varela Martínez, I., Villalba Requena, A., García-Marqués, J., Aguilera, A.,
    Castro, D. S., Hippenmeyer, S., &#38; Nieto, M. (2026). Early fate diversification
    of radial glial progenitors during corticogenesis. <i>Science Advances</i>. AAAS.
    <a href="https://doi.org/10.1126/sciadv.adw5487">https://doi.org/10.1126/sciadv.adw5487</a>
  chicago: Varela Martínez, Irene, Ana Villalba Requena, Jorge García-Marqués, Alfonso
    Aguilera, Diogo S. Castro, Simon Hippenmeyer, and Marta Nieto. “Early Fate Diversification
    of Radial Glial Progenitors during Corticogenesis.” <i>Science Advances</i>. AAAS,
    2026. <a href="https://doi.org/10.1126/sciadv.adw5487">https://doi.org/10.1126/sciadv.adw5487</a>.
  ieee: I. Varela Martínez <i>et al.</i>, “Early fate diversification of radial glial
    progenitors during corticogenesis,” <i>Science Advances</i>, vol. 12, no. 32.
    AAAS, p. eadw5487, 2026.
  ista: Varela Martínez I, Villalba Requena A, García-Marqués J, Aguilera A, Castro
    DS, Hippenmeyer S, Nieto M. 2026. Early fate diversification of radial glial progenitors
    during corticogenesis. Science Advances. 12(32), eadw5487.
  mla: Varela Martínez, Irene, et al. “Early Fate Diversification of Radial Glial
    Progenitors during Corticogenesis.” <i>Science Advances</i>, vol. 12, no. 32,
    AAAS, 2026, p. eadw5487, doi:<a href="https://doi.org/10.1126/sciadv.adw5487">10.1126/sciadv.adw5487</a>.
  short: I. Varela Martínez, A. Villalba Requena, J. García-Marqués, A. Aguilera,
    D.S. Castro, S. Hippenmeyer, M. Nieto, Science Advances 12 (2026) eadw5487.
das_tickbox: '1'
dataavailabilitystatement: 'All data and code needed to evaluate and reproduce the
  results in the paper are present in the paper and/or the Supplementary Materials.
  Source data underlying all figures (including the clonal atlas) are provided in
  the Supplementary Materials. RnA-seq analysis code has been deposited in Zenodo
  (dOi: 10.5281/zenodo.14609057). this study did not generate new materials.'
date_created: 2026-08-16T22:01:43Z
date_published: 2026-08-07T00:00:00Z
date_updated: 2026-08-20T05:45:28Z
day: '07'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1126/sciadv.adw5487
external_id:
  pmid:
  - '42555737'
file:
- access_level: open_access
  checksum: 487c3703387080e8f3c4675d67763f0e
  content_type: application/pdf
  creator: dernst
  date_created: 2026-08-20T05:39:32Z
  date_updated: 2026-08-20T05:39:32Z
  file_id: '22738'
  file_name: 2026_ScienceAdv_VarelaMartinez.pdf
  file_size: 3056744
  relation: main_file
  success: 1
file_date_updated: 2026-08-20T05:39:32Z
has_accepted_license: '1'
intvolume: '        12'
issue: '32'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: eadw5487
pmid: 1
publication: Science Advances
publication_identifier:
  eissn:
  - 2375-2548
publication_status: published
publisher: AAAS
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Early fate diversification of radial glial progenitors during corticogenesis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2026'
...