---
_id: '944'
abstract:
- lang: eng
  text: The concerted production of neurons and glia by neural stem cells (NSCs) is
    essential for neural circuit assembly. In the developing cerebral cortex, radial
    glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia
    lineages. RGP proliferation behavior shows a high degree of non-stochasticity,
    thus a deterministic characteristic of neuron and glia production. However, the
    cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics
    in neurogenesis and glia generation remain unknown. By using mosaic analysis with
    double markers (MADM)-based genetic paradigms enabling the sparse and global knockout
    with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory
    component. We uncover Lgl1-dependent tissue-wide community effects required for
    embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling
    RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that
    NSC-mediated neuron and glia production is tightly regulated through the concerted
    interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
article_processing_charge: No
author:
- first_name: Robert J
  full_name: Beattie, Robert J
  id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
  last_name: Beattie
  orcid: 0000-0002-8483-8753
- first_name: Maria P
  full_name: Postiglione, Maria P
  id: 2C67902A-F248-11E8-B48F-1D18A9856A87
  last_name: Postiglione
- first_name: Laura
  full_name: Burnett, Laura
  id: 3B717F68-F248-11E8-B48F-1D18A9856A87
  last_name: Burnett
  orcid: 0000-0002-8937-410X
- first_name: Susanne
  full_name: Laukoter, Susanne
  id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
  last_name: Laukoter
  orcid: 0000-0002-7903-3010
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
  orcid: 0000-0002-7462-0048
- first_name: Guanxi
  full_name: Xiao, Guanxi
  last_name: Xiao
- first_name: Olga
  full_name: Klezovitch, Olga
  last_name: Klezovitch
- first_name: Valeri
  full_name: Vasioukhin, Valeri
  last_name: Vasioukhin
- first_name: Troy
  full_name: Ghashghaei, Troy
  last_name: Ghashghaei
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Beattie RJ, Postiglione MP, Burnett L, et al. Mosaic analysis with double markers
    reveals distinct sequential functions of Lgl1 in neural stem cells. <i>Neuron</i>.
    2017;94(3):517-533.e3. doi:<a href="https://doi.org/10.1016/j.neuron.2017.04.012">10.1016/j.neuron.2017.04.012</a>
  apa: Beattie, R. J., Postiglione, M. P., Burnett, L., Laukoter, S., Streicher, C.,
    Pauler, F., … Hippenmeyer, S. (2017). Mosaic analysis with double markers reveals
    distinct sequential functions of Lgl1 in neural stem cells. <i>Neuron</i>. Cell
    Press. <a href="https://doi.org/10.1016/j.neuron.2017.04.012">https://doi.org/10.1016/j.neuron.2017.04.012</a>
  chicago: Beattie, Robert J, Maria P Postiglione, Laura Burnett, Susanne Laukoter,
    Carmen Streicher, Florian Pauler, Guanxi Xiao, et al. “Mosaic Analysis with Double
    Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells.” <i>Neuron</i>.
    Cell Press, 2017. <a href="https://doi.org/10.1016/j.neuron.2017.04.012">https://doi.org/10.1016/j.neuron.2017.04.012</a>.
  ieee: R. J. Beattie <i>et al.</i>, “Mosaic analysis with double markers reveals
    distinct sequential functions of Lgl1 in neural stem cells,” <i>Neuron</i>, vol.
    94, no. 3. Cell Press, p. 517–533.e3, 2017.
  ista: Beattie RJ, Postiglione MP, Burnett L, Laukoter S, Streicher C, Pauler F,
    Xiao G, Klezovitch O, Vasioukhin V, Ghashghaei T, Hippenmeyer S. 2017. Mosaic
    analysis with double markers reveals distinct sequential functions of Lgl1 in
    neural stem cells. Neuron. 94(3), 517–533.e3.
  mla: Beattie, Robert J., et al. “Mosaic Analysis with Double Markers Reveals Distinct
    Sequential Functions of Lgl1 in Neural Stem Cells.” <i>Neuron</i>, vol. 94, no.
    3, Cell Press, 2017, p. 517–533.e3, doi:<a href="https://doi.org/10.1016/j.neuron.2017.04.012">10.1016/j.neuron.2017.04.012</a>.
  short: R.J. Beattie, M.P. Postiglione, L. Burnett, S. Laukoter, C. Streicher, F.
    Pauler, G. Xiao, O. Klezovitch, V. Vasioukhin, T. Ghashghaei, S. Hippenmeyer,
    Neuron 94 (2017) 517–533.e3.
date_created: 2018-12-11T11:49:20Z
date_published: 2017-05-03T00:00:00Z
date_updated: 2023-09-26T15:37:02Z
day: '03'
department:
- _id: SiHi
- _id: MaJö
doi: 10.1016/j.neuron.2017.04.012
ec_funded: 1
external_id:
  isi:
  - '000400466700011'
intvolume: '        94'
isi: 1
issue: '3'
language:
- iso: eng
month: '05'
oa_version: None
page: 517 - 533.e3
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618444'
  name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 25D7962E-B435-11E9-9278-68D0E5697425
  grant_number: RGP0053/2014
  name: Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal
    Level
publication: Neuron
publication_identifier:
  issn:
  - '08966273'
publication_status: published
publisher: Cell Press
publist_id: '6473'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mosaic analysis with double markers reveals distinct sequential functions of
  Lgl1 in neural stem cells
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 94
year: '2017'
...
---
_id: '1899'
abstract:
- lang: eng
  text: Asymmetric cell divisions allow stem cells to balance proliferation and differentiation.
    During embryogenesis, murine epidermis expands rapidly from a single layer of
    unspecified basal layer progenitors to a stratified, differentiated epithelium.
    Morphogenesis involves perpendicular (asymmetric) divisions and the spindle orientation
    protein LGN, but little is known about how the apical localization of LGN is regulated.
    Here, we combine conventional genetics and lentiviral-mediated in vivo RNAi to
    explore the functions of the LGN-interacting proteins Par3, mInsc and Gα i3. Whereas
    loss of each gene alone leads to randomized division angles, combined loss of
    Gnai3 and mInsc causes a phenotype of mostly planar divisions, akin to loss of
    LGN. These findings lend experimental support for the hitherto untested model
    that Par3-mInsc and Gα i3 act cooperatively to polarize LGN and promote perpendicular
    divisions. Finally, we uncover a developmental switch between delamination-driven
    early stratification and spindle-orientation-dependent differentiation that occurs
    around E15, revealing a two-step mechanism underlying epidermal maturation.
article_processing_charge: No
article_type: original
author:
- first_name: Scott
  full_name: Williams, Scott
  last_name: Williams
- first_name: Lyndsay
  full_name: Ratliff, Lyndsay
  last_name: Ratliff
- first_name: Maria P
  full_name: Postiglione, Maria P
  id: 2C67902A-F248-11E8-B48F-1D18A9856A87
  last_name: Postiglione
- first_name: Juergen
  full_name: Knoblich, Juergen
  last_name: Knoblich
- first_name: Elaine
  full_name: Fuchs, Elaine
  last_name: Fuchs
citation:
  ama: Williams S, Ratliff L, Postiglione MP, Knoblich J, Fuchs E. Par3-mInsc and
    Gα i3 cooperate to promote oriented epidermal cell divisions through LGN. <i>Nature
    Cell Biology</i>. 2014;16(8):758-769. doi:<a href="https://doi.org/10.1038/ncb3001">10.1038/ncb3001</a>
  apa: Williams, S., Ratliff, L., Postiglione, M. P., Knoblich, J., &#38; Fuchs, E.
    (2014). Par3-mInsc and Gα i3 cooperate to promote oriented epidermal cell divisions
    through LGN. <i>Nature Cell Biology</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/ncb3001">https://doi.org/10.1038/ncb3001</a>
  chicago: Williams, Scott, Lyndsay Ratliff, Maria P Postiglione, Juergen Knoblich,
    and Elaine Fuchs. “Par3-MInsc and Gα I3 Cooperate to Promote Oriented Epidermal
    Cell Divisions through LGN.” <i>Nature Cell Biology</i>. Nature Publishing Group,
    2014. <a href="https://doi.org/10.1038/ncb3001">https://doi.org/10.1038/ncb3001</a>.
  ieee: S. Williams, L. Ratliff, M. P. Postiglione, J. Knoblich, and E. Fuchs, “Par3-mInsc
    and Gα i3 cooperate to promote oriented epidermal cell divisions through LGN,”
    <i>Nature Cell Biology</i>, vol. 16, no. 8. Nature Publishing Group, pp. 758–769,
    2014.
  ista: Williams S, Ratliff L, Postiglione MP, Knoblich J, Fuchs E. 2014. Par3-mInsc
    and Gα i3 cooperate to promote oriented epidermal cell divisions through LGN.
    Nature Cell Biology. 16(8), 758–769.
  mla: Williams, Scott, et al. “Par3-MInsc and Gα I3 Cooperate to Promote Oriented
    Epidermal Cell Divisions through LGN.” <i>Nature Cell Biology</i>, vol. 16, no.
    8, Nature Publishing Group, 2014, pp. 758–69, doi:<a href="https://doi.org/10.1038/ncb3001">10.1038/ncb3001</a>.
  short: S. Williams, L. Ratliff, M.P. Postiglione, J. Knoblich, E. Fuchs, Nature
    Cell Biology 16 (2014) 758–769.
date_created: 2018-12-11T11:54:36Z
date_published: 2014-07-13T00:00:00Z
date_updated: 2021-01-12T06:53:55Z
day: '13'
department:
- _id: SiHi
doi: 10.1038/ncb3001
external_id:
  pmid:
  - '25016959'
intvolume: '        16'
issue: '8'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159251/
month: '07'
oa: 1
oa_version: Submitted Version
page: 758 - 769
pmid: 1
publication: Nature Cell Biology
publication_status: published
publisher: Nature Publishing Group
publist_id: '5196'
quality_controlled: '1'
scopus_import: 1
status: public
title: Par3-mInsc and Gα i3 cooperate to promote oriented epidermal cell divisions
  through LGN
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2014'
...
---
_id: '2022'
abstract:
- lang: eng
  text: Radial glial progenitors (RGPs) are responsible for producing nearly all neocortical
    neurons. To gain insight into the patterns of RGP division and neuron production,
    we quantitatively analyzed excitatory neuron genesis in the mouse neocortex using
    Mosaic Analysis with Double Markers, which provides single-cell resolution of
    progenitor division patterns and potential in vivo. We found that RGPs progress
    through a coherent program in which their proliferative potential diminishes in
    a predictable manner. Upon entry into the neurogenic phase, individual RGPs produce
    ∼8–9 neurons distributed in both deep and superficial layers, indicating a unitary
    output in neuronal production. Removal of OTX1, a transcription factor transiently
    expressed in RGPs, results in both deep- and superficial-layer neuron loss and
    a reduction in neuronal unit size. Moreover, ∼1/6 of neurogenic RGPs proceed to
    produce glia. These results suggest that progenitor behavior and histogenesis
    in the mammalian neocortex conform to a remarkably orderly and deterministic program.
author:
- first_name: Peng
  full_name: Gao, Peng
  last_name: Gao
- first_name: Maria P
  full_name: Postiglione, Maria P
  id: 2C67902A-F248-11E8-B48F-1D18A9856A87
  last_name: Postiglione
- first_name: Teresa
  full_name: Krieger, Teresa
  last_name: Krieger
- first_name: Luisirene
  full_name: Hernandez, Luisirene
  last_name: Hernandez
- first_name: Chao
  full_name: Wang, Chao
  last_name: Wang
- first_name: Zhi
  full_name: Han, Zhi
  last_name: Han
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Ekaterina
  full_name: Papusheva, Ekaterina
  id: 41DB591E-F248-11E8-B48F-1D18A9856A87
  last_name: Papusheva
- first_name: Ryan
  full_name: Insolera, Ryan
  last_name: Insolera
- first_name: Kritika
  full_name: Chugh, Kritika
  last_name: Chugh
- first_name: Oren
  full_name: Kodish, Oren
  last_name: Kodish
- first_name: Kun
  full_name: Huang, Kun
  last_name: Huang
- first_name: Benjamin
  full_name: Simons, Benjamin
  last_name: Simons
- first_name: Liqun
  full_name: Luo, Liqun
  last_name: Luo
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
- first_name: Song
  full_name: Shi, Song
  last_name: Shi
citation:
  ama: Gao P, Postiglione MP, Krieger T, et al. Deterministic progenitor behavior
    and unitary production of neurons in the neocortex. <i>Cell</i>. 2014;159(4):775-788.
    doi:<a href="https://doi.org/10.1016/j.cell.2014.10.027">10.1016/j.cell.2014.10.027</a>
  apa: Gao, P., Postiglione, M. P., Krieger, T., Hernandez, L., Wang, C., Han, Z.,
    … Shi, S. (2014). Deterministic progenitor behavior and unitary production of
    neurons in the neocortex. <i>Cell</i>. Cell Press. <a href="https://doi.org/10.1016/j.cell.2014.10.027">https://doi.org/10.1016/j.cell.2014.10.027</a>
  chicago: Gao, Peng, Maria P Postiglione, Teresa Krieger, Luisirene Hernandez, Chao
    Wang, Zhi Han, Carmen Streicher, et al. “Deterministic Progenitor Behavior and
    Unitary Production of Neurons in the Neocortex.” <i>Cell</i>. Cell Press, 2014.
    <a href="https://doi.org/10.1016/j.cell.2014.10.027">https://doi.org/10.1016/j.cell.2014.10.027</a>.
  ieee: P. Gao <i>et al.</i>, “Deterministic progenitor behavior and unitary production
    of neurons in the neocortex,” <i>Cell</i>, vol. 159, no. 4. Cell Press, pp. 775–788,
    2014.
  ista: Gao P, Postiglione MP, Krieger T, Hernandez L, Wang C, Han Z, Streicher C,
    Papusheva E, Insolera R, Chugh K, Kodish O, Huang K, Simons B, Luo L, Hippenmeyer
    S, Shi S. 2014. Deterministic progenitor behavior and unitary production of neurons
    in the neocortex. Cell. 159(4), 775–788.
  mla: Gao, Peng, et al. “Deterministic Progenitor Behavior and Unitary Production
    of Neurons in the Neocortex.” <i>Cell</i>, vol. 159, no. 4, Cell Press, 2014,
    pp. 775–88, doi:<a href="https://doi.org/10.1016/j.cell.2014.10.027">10.1016/j.cell.2014.10.027</a>.
  short: P. Gao, M.P. Postiglione, T. Krieger, L. Hernandez, C. Wang, Z. Han, C. Streicher,
    E. Papusheva, R. Insolera, K. Chugh, O. Kodish, K. Huang, B. Simons, L. Luo, S.
    Hippenmeyer, S. Shi, Cell 159 (2014) 775–788.
date_created: 2018-12-11T11:55:16Z
date_published: 2014-11-06T00:00:00Z
date_updated: 2021-01-12T06:54:47Z
day: '06'
ddc:
- '570'
department:
- _id: SiHi
- _id: Bio
doi: 10.1016/j.cell.2014.10.027
ec_funded: 1
file:
- access_level: open_access
  checksum: 6c5de8329bb2ffa71cba9fda750f14ce
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:08:47Z
  date_updated: 2020-07-14T12:45:25Z
  file_id: '4709'
  file_name: IST-2016-423-v1+1_1-s2.0-S0092867414013154-main.pdf
  file_size: 4435787
  relation: main_file
file_date_updated: 2020-07-14T12:45:25Z
has_accepted_license: '1'
intvolume: '       159'
issue: '4'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: 775 - 788
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618444'
  name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 25D7962E-B435-11E9-9278-68D0E5697425
  grant_number: RGP0053/2014
  name: Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal
    Level
publication: Cell
publication_status: published
publisher: Cell Press
publist_id: '5050'
pubrep_id: '423'
quality_controlled: '1'
scopus_import: 1
status: public
title: Deterministic progenitor behavior and unitary production of neurons in the
  neocortex
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: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 159
year: '2014'
...
---
_id: '2175'
abstract:
- lang: eng
  text: The cerebral cortex, the seat of our cognitive abilities, is composed of an
    intricate network of billions of excitatory projection and inhibitory interneurons.
    Postmitotic cortical neurons are generated by a diverse set of neural stem cell
    progenitors within dedicated zones and defined periods of neurogenesis during
    embryonic development. Disruptions in neurogenesis can lead to alterations in
    the neuronal cytoarchitecture, which is thought to represent a major underlying
    cause for several neurological disorders, including microcephaly, autism and epilepsy.
    Although a number of signaling pathways regulating neurogenesis have been described,
    the precise cellular and molecular mechanisms regulating the functional neural
    stem cell properties in cortical neurogenesis remain unclear. Here, we discuss
    the most up-to-date strategies to monitor the fundamental mechanistic parameters
    of neuronal progenitor proliferation, and recent advances deciphering the logic
    and dynamics of neurogenesis.
article_processing_charge: No
author:
- first_name: Maria P
  full_name: Postiglione, Maria P
  id: 2C67902A-F248-11E8-B48F-1D18A9856A87
  last_name: Postiglione
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: 'Postiglione MP, Hippenmeyer S. Monitoring neurogenesis in the cerebral cortex:
    an update. <i>Future Neurology</i>. 2014;9(3):323-340. doi:<a href="https://doi.org/10.2217/fnl.14.18">10.2217/fnl.14.18</a>'
  apa: 'Postiglione, M. P., &#38; Hippenmeyer, S. (2014). Monitoring neurogenesis
    in the cerebral cortex: an update. <i>Future Neurology</i>. Future Science Group.
    <a href="https://doi.org/10.2217/fnl.14.18">https://doi.org/10.2217/fnl.14.18</a>'
  chicago: 'Postiglione, Maria P, and Simon Hippenmeyer. “Monitoring Neurogenesis
    in the Cerebral Cortex: An Update.” <i>Future Neurology</i>. Future Science Group,
    2014. <a href="https://doi.org/10.2217/fnl.14.18">https://doi.org/10.2217/fnl.14.18</a>.'
  ieee: 'M. P. Postiglione and S. Hippenmeyer, “Monitoring neurogenesis in the cerebral
    cortex: an update,” <i>Future Neurology</i>, vol. 9, no. 3. Future Science Group,
    pp. 323–340, 2014.'
  ista: 'Postiglione MP, Hippenmeyer S. 2014. Monitoring neurogenesis in the cerebral
    cortex: an update. Future Neurology. 9(3), 323–340.'
  mla: 'Postiglione, Maria P., and Simon Hippenmeyer. “Monitoring Neurogenesis in
    the Cerebral Cortex: An Update.” <i>Future Neurology</i>, vol. 9, no. 3, Future
    Science Group, 2014, pp. 323–40, doi:<a href="https://doi.org/10.2217/fnl.14.18">10.2217/fnl.14.18</a>.'
  short: M.P. Postiglione, S. Hippenmeyer, Future Neurology 9 (2014) 323–340.
date_created: 2018-12-11T11:56:09Z
date_published: 2014-05-01T00:00:00Z
date_updated: 2023-10-17T08:34:27Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.2217/fnl.14.18
ec_funded: 1
file:
- access_level: open_access
  checksum: ba06659ecadabceec9a37dd8c4586dce
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:10:25Z
  date_updated: 2020-07-14T12:45:31Z
  file_id: '4812'
  file_name: IST-2016-528-v1+1_fnl.14.18.pdf
  file_size: 3848424
  relation: main_file
file_date_updated: 2020-07-14T12:45:31Z
has_accepted_license: '1'
intvolume: '         9'
issue: '3'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '05'
oa: 1
oa_version: Published Version
page: 323 - 340
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618444'
  name: Molecular Mechanisms of Cerebral Cortex Development
publication: Future Neurology
publication_identifier:
  eissn:
  - 1748-6971
  issn:
  - 1479-6708
publication_status: published
publisher: Future Science Group
publist_id: '4806'
pubrep_id: '528'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Monitoring neurogenesis in the cerebral cortex: an update'
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2014'
...