Cargando…

Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome

Progenitor cells in the cerebral cortex undergo dynamic cellular and molecular changes during development. Sall1 is a putative transcription factor that is highly expressed in progenitor cells during development. In humans, the autosomal dominant developmental disorder Townes-Brocks syndrome (TBS) i...

Descripción completa

Detalles Bibliográficos
Autores principales: Harrison, Susan J., Nishinakamura, Ryuichi, Jones, Kevin R., Monaghan, A. Paula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Limited 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339829/
https://www.ncbi.nlm.nih.gov/pubmed/22228756
http://dx.doi.org/10.1242/dmm.002873
_version_ 1782231424308346880
author Harrison, Susan J.
Nishinakamura, Ryuichi
Jones, Kevin R.
Monaghan, A. Paula
author_facet Harrison, Susan J.
Nishinakamura, Ryuichi
Jones, Kevin R.
Monaghan, A. Paula
author_sort Harrison, Susan J.
collection PubMed
description Progenitor cells in the cerebral cortex undergo dynamic cellular and molecular changes during development. Sall1 is a putative transcription factor that is highly expressed in progenitor cells during development. In humans, the autosomal dominant developmental disorder Townes-Brocks syndrome (TBS) is associated with mutations of the SALL1 gene. TBS is characterized by renal, anal, limb and auditory abnormalities. Although neural deficits have not been recognized as a diagnostic characteristic of the disease, ∼10% of patients exhibit neural or behavioral abnormalities. We demonstrate that, in addition to being expressed in peripheral organs, Sall1 is robustly expressed in progenitor cells of the central nervous system in mice. Both classical- and conditional-knockout mouse studies indicate that the cerebral cortex is particularly sensitive to loss of Sall1. In the absence of Sall1, both the surface area and depth of the cerebral cortex were decreased at embryonic day 18.5 (E18.5). These deficiencies are associated with changes in progenitor cell properties during development. In early cortical progenitor cells, Sall1 promotes proliferative over neurogenic division, whereas, at later developmental stages, Sall1 regulates the production and differentiation of intermediate progenitor cells. Furthermore, Sall1 influences the temporal specification of cortical laminae. These findings present novel insights into the function of Sall1 in the developing mouse cortex and provide avenues for future research into potential neural deficits in individuals with TBS.
format Online
Article
Text
id pubmed-3339829
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher The Company of Biologists Limited
record_format MEDLINE/PubMed
spelling pubmed-33398292012-05-02 Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome Harrison, Susan J. Nishinakamura, Ryuichi Jones, Kevin R. Monaghan, A. Paula Dis Model Mech Research Article Progenitor cells in the cerebral cortex undergo dynamic cellular and molecular changes during development. Sall1 is a putative transcription factor that is highly expressed in progenitor cells during development. In humans, the autosomal dominant developmental disorder Townes-Brocks syndrome (TBS) is associated with mutations of the SALL1 gene. TBS is characterized by renal, anal, limb and auditory abnormalities. Although neural deficits have not been recognized as a diagnostic characteristic of the disease, ∼10% of patients exhibit neural or behavioral abnormalities. We demonstrate that, in addition to being expressed in peripheral organs, Sall1 is robustly expressed in progenitor cells of the central nervous system in mice. Both classical- and conditional-knockout mouse studies indicate that the cerebral cortex is particularly sensitive to loss of Sall1. In the absence of Sall1, both the surface area and depth of the cerebral cortex were decreased at embryonic day 18.5 (E18.5). These deficiencies are associated with changes in progenitor cell properties during development. In early cortical progenitor cells, Sall1 promotes proliferative over neurogenic division, whereas, at later developmental stages, Sall1 regulates the production and differentiation of intermediate progenitor cells. Furthermore, Sall1 influences the temporal specification of cortical laminae. These findings present novel insights into the function of Sall1 in the developing mouse cortex and provide avenues for future research into potential neural deficits in individuals with TBS. The Company of Biologists Limited 2012-05 2011-12-22 /pmc/articles/PMC3339829/ /pubmed/22228756 http://dx.doi.org/10.1242/dmm.002873 Text en © 2012. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms
spellingShingle Research Article
Harrison, Susan J.
Nishinakamura, Ryuichi
Jones, Kevin R.
Monaghan, A. Paula
Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome
title Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome
title_full Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome
title_fullStr Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome
title_full_unstemmed Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome
title_short Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome
title_sort sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in townes-brocks syndrome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339829/
https://www.ncbi.nlm.nih.gov/pubmed/22228756
http://dx.doi.org/10.1242/dmm.002873
work_keys_str_mv AT harrisonsusanj sall1regulatescorticalneurogenesisandlaminarfatespecificationinmiceimplicationsforneuralabnormalitiesintownesbrockssyndrome
AT nishinakamuraryuichi sall1regulatescorticalneurogenesisandlaminarfatespecificationinmiceimplicationsforneuralabnormalitiesintownesbrockssyndrome
AT joneskevinr sall1regulatescorticalneurogenesisandlaminarfatespecificationinmiceimplicationsforneuralabnormalitiesintownesbrockssyndrome
AT monaghanapaula sall1regulatescorticalneurogenesisandlaminarfatespecificationinmiceimplicationsforneuralabnormalitiesintownesbrockssyndrome