---
OA_place: repository
OA_type: green
_id: '21963'
abstract:
- lang: eng
  text: The cerebral cortex consists of immense numbers of neuronal and glial cell-types
    derived from radial glial progenitor (RGP) cells. How RGPs generate appropriate
    quantities of distinct cortical cell-types to safeguard a brain of correct size,
    is not well understood. However, genetic aberration in human, including mutations
    in PTEN, lead to cortical malformation such as macrocephaly, albeit with unknown
    etiology. Here we utilized Mosaic Analysis with Double Markers (MADM)-based clonal
    analysis and single cell phenotyping to decipher the role of Pten in neurogenic
    and gliogenic RGP lineage progression during cortical ontogeny. While neurogenic
    RGP lineage progression and projection neuron production was moderately altered
    in the absence of Pten, cortical astrocyte production was drastically increased.
    Through genetic epistasis experiments we show that the loss of Pten uncouples
    astrocyte generation from essential growth factor signaling hubs, funneling into
    MAPK. Collectively, our results suggest that Pten regulates RGP lineage progression
    with distinct sequential functions in cortical projection neurogenesis and astrocyte
    production to ensure the emergence of a correctly-sized cerebral cortex.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: "We thank Kay-Uwe Wagner (Wayne State University) for generously
  sharing Jak1/2–flox mouse lines; A.\r\nSommer (VBCF GmbH, NGS Unit) for technical
  support; N. Kim, V. Mick, S. Schnabl, S. Gobeil, and L.\r\nAndersen for technical
  assistance; all members of the Hippenmeyer lab for discussion and B. Novitch for\r\ncomments
  on earlier versions of the manuscript. This research was supported by the Scientific
  Service Units\r\n(SSU) of IST Austria through resources provided by the Imaging
  and Optics Facility (IOF), Lab Support-\r\n(LSF) and Preclinical Facilities (PCF).
  O.A.M received support from the Austrian Academy of Sciences\r\nÖAW (DOC 186584),
  and N.A. from FWF Elise Richter Program (Grant V1041T). This work was also\r\nsupported
  by IST Austria institutional funds; FWF SFB F78 (Neuro Stem Modulation) to S.H.,
  and the\r\nEuropean Research Council (ERC) under the European Union’s Horizon 2020
  research and innovation\r\nprogramme (grant agreement No 725780 LinPro) to S.H."
article_processing_charge: No
author:
- first_name: Osvaldo
  full_name: Miranda, Osvaldo
  id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
  last_name: Miranda
  orcid: 0000-0001-6618-6889
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
  orcid: 0000-0002-7462-0048
- first_name: Amarbayasgalan
  full_name: Davaatseren, Amarbayasgalan
  id: 70ADC922-B424-11E9-99E3-BA18E6697425
  last_name: Davaatseren
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- 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: Anna-Magdalena
  full_name: Heger, Anna-Magdalena
  id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
  last_name: Heger
- first_name: Corentine
  full_name: Marie, Corentine
  last_name: Marie
- first_name: Bassem A.
  full_name: Hassan, Bassem A.
  last_name: Hassan
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Miranda O, Contreras X, Pauler F, et al. Pten orchestrates neurogenic radial
    glia lineage progression and tunes neocortical astrocyte production. <i>bioRxiv</i>.
    doi:<a href="https://doi.org/10.64898/2026.05.01.722191">10.64898/2026.05.01.722191</a>
  apa: Miranda, O., Contreras, X., Pauler, F., Davaatseren, A., Amberg, N., Streicher,
    C., … Hippenmeyer, S. (n.d.). Pten orchestrates neurogenic radial glia lineage
    progression and tunes neocortical astrocyte production. <i>bioRxiv</i>. <a href="https://doi.org/10.64898/2026.05.01.722191">https://doi.org/10.64898/2026.05.01.722191</a>
  chicago: Miranda, Osvaldo, Ximena Contreras, Florian Pauler, Amarbayasgalan Davaatseren,
    Nicole Amberg, Carmen Streicher, Ana Villalba Requena, et al. “Pten Orchestrates
    Neurogenic Radial Glia Lineage Progression and Tunes Neocortical Astrocyte Production.”
    <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.64898/2026.05.01.722191">https://doi.org/10.64898/2026.05.01.722191</a>.
  ieee: O. Miranda <i>et al.</i>, “Pten orchestrates neurogenic radial glia lineage
    progression and tunes neocortical astrocyte production,” <i>bioRxiv</i>. .
  ista: Miranda O, Contreras X, Pauler F, Davaatseren A, Amberg N, Streicher C, Villalba
    Requena A, Heger A-M, Marie C, Hassan BA, Rülicke T, Hippenmeyer S. Pten orchestrates
    neurogenic radial glia lineage progression and tunes neocortical astrocyte production.
    bioRxiv, <a href="https://doi.org/10.64898/2026.05.01.722191">10.64898/2026.05.01.722191</a>.
  mla: Miranda, Osvaldo, et al. “Pten Orchestrates Neurogenic Radial Glia Lineage
    Progression and Tunes Neocortical Astrocyte Production.” <i>BioRxiv</i>, doi:<a
    href="https://doi.org/10.64898/2026.05.01.722191">10.64898/2026.05.01.722191</a>.
  short: O. Miranda, X. Contreras, F. Pauler, A. Davaatseren, N. Amberg, C. Streicher,
    A. Villalba Requena, A.-M. Heger, C. Marie, B.A. Hassan, T. Rülicke, S. Hippenmeyer,
    BioRxiv (n.d.).
corr_author: '1'
date_created: 2026-06-09T08:08:53Z
date_published: 2026-05-05T00:00:00Z
date_updated: 2026-06-16T08:57:20Z
day: '05'
ddc:
- '570'
department:
- _id: SiHi
- _id: PreCl
- _id: GradSch
doi: 10.64898/2026.05.01.722191
ec_funded: 1
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.64898/2026.05.01.722191
month: '05'
oa: 1
oa_version: Preprint
project:
- _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
- _id: 260018B0-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '725780'
  name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: bioRxiv
publication_status: submitted
status: public
title: Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical
  astrocyte production
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
_id: '9603'
abstract:
- lang: eng
  text: Mosaic analysis with double markers (MADM) offers one approach to visualize
    and concomitantly manipulate genetically defined cells in mice with single-cell
    resolution. MADM applications include the analysis of lineage, single-cell morphology
    and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous
    gene functions in vivo in health and disease. Yet, MADM can only be applied to
    <25% of all mouse genes on select chromosomes to date. To overcome this limitation,
    we generate transgenic mice with knocked-in MADM cassettes near the centromeres
    of all 19 autosomes and validate their use across organs. With this resource,
    >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic
    analysis. Beyond a proof of principle, we apply our MADM library to systematically
    trace sister chromatid segregation in distinct mitotic cell lineages. We find
    striking chromosome-specific biases in segregation patterns, reflecting a putative
    mechanism for the asymmetric segregation of genetic determinants in somatic stem
    cell division.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Bioimaging, Life Science, and Pre-Clinical Facilities
  at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain,
  M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance;
  R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of
  the Hippenmeyer lab for discussion. This work was supported by National Institutes
  of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator
  of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is
  a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This
  work also received support from IST Austria institutional funds , FWF SFB F78 to
  S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh
  Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H.,
  and the European Research Council (ERC) under the European Union’s Horizon 2020
  Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.
article_number: '109274'
article_processing_charge: No
article_type: original
author:
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Amarbayasgalan
  full_name: Davaatseren, Amarbayasgalan
  id: 70ADC922-B424-11E9-99E3-BA18E6697425
  last_name: Davaatseren
- first_name: Andi H
  full_name: Hansen, Andi H
  id: 38853E16-F248-11E8-B48F-1D18A9856A87
  last_name: Hansen
- first_name: Johanna
  full_name: Sonntag, Johanna
  id: 32FE7D7C-F248-11E8-B48F-1D18A9856A87
  last_name: Sonntag
- first_name: Lill
  full_name: Andersen, Lill
  last_name: Andersen
- first_name: Tina
  full_name: Bernthaler, Tina
  last_name: Bernthaler
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Anna-Magdalena
  full_name: Heger, Anna-Magdalena
  id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
  last_name: Heger
- first_name: Randy L.
  full_name: Johnson, Randy L.
  last_name: Johnson
- first_name: Lindsay A.
  full_name: Schwarz, Lindsay A.
  last_name: Schwarz
- first_name: Liqun
  full_name: Luo, Liqun
  last_name: Luo
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM
    mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. 2021;35(12).
    doi:<a href="https://doi.org/10.1016/j.celrep.2021.109274">10.1016/j.celrep.2021.109274</a>
  apa: Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen,
    L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell
    genetic mosaic analysis. <i>Cell Reports</i>. Cell Press. <a href="https://doi.org/10.1016/j.celrep.2021.109274">https://doi.org/10.1016/j.celrep.2021.109274</a>
  chicago: Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen,
    Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library
    of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>. Cell
    Press, 2021. <a href="https://doi.org/10.1016/j.celrep.2021.109274">https://doi.org/10.1016/j.celrep.2021.109274</a>.
  ieee: X. Contreras <i>et al.</i>, “A genome-wide library of MADM mice for single-cell
    genetic mosaic analysis,” <i>Cell Reports</i>, vol. 35, no. 12. Cell Press, 2021.
  ista: Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler
    T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer
    S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis.
    Cell Reports. 35(12), 109274.
  mla: Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell
    Genetic Mosaic Analysis.” <i>Cell Reports</i>, vol. 35, no. 12, 109274, Cell Press,
    2021, doi:<a href="https://doi.org/10.1016/j.celrep.2021.109274">10.1016/j.celrep.2021.109274</a>.
  short: X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen,
    T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo,
    T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).
date_created: 2021-06-27T22:01:48Z
date_published: 2021-06-22T00:00:00Z
date_updated: 2026-04-02T14:04:28Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
- _id: LoSw
- _id: PreCl
doi: 10.1016/j.celrep.2021.109274
ec_funded: 1
external_id:
  isi:
  - '000664463600016'
  pmid:
  - '34161767'
file:
- access_level: open_access
  checksum: d49520fdcbbb5c2f883bddb67cee5d77
  content_type: application/pdf
  creator: asandaue
  date_created: 2021-06-28T14:06:24Z
  date_updated: 2021-06-28T14:06:24Z
  file_id: '9613'
  file_name: 2021_CellReports_Contreras.pdf
  file_size: 7653149
  relation: main_file
  success: 1
file_date_updated: 2021-06-28T14:06:24Z
has_accepted_license: '1'
intvolume: '        35'
isi: 1
issue: '12'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
  grant_number: '24812'
  name: Molecular mechanisms of radial neuronal migration
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618444'
  name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '725780'
  name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Cell Reports
publication_identifier:
  eissn:
  - 2211-1247
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/
scopus_import: '1'
status: public
title: A genome-wide library of MADM mice for single-cell genetic mosaic analysis
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 35
year: '2021'
...