Cargando…

­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system

BACKGROUND: Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in the development and function of multiple organs and organ systems, including the central nervous system (CNS). FGF signaling via FGFR1, one of the three FGFRs expressed in the CNS, stimulates proliferation of st...

Descripción completa

Detalles Bibliográficos
Autores principales: Collette, Jantzen C., Choubey, Lisha, Smith, Karen Müller
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493973/
https://www.ncbi.nlm.nih.gov/pubmed/28674667
http://dx.doi.org/10.7717/peerj.3519
_version_ 1783247600613326848
author Collette, Jantzen C.
Choubey, Lisha
Smith, Karen Müller
author_facet Collette, Jantzen C.
Choubey, Lisha
Smith, Karen Müller
author_sort Collette, Jantzen C.
collection PubMed
description BACKGROUND: Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in the development and function of multiple organs and organ systems, including the central nervous system (CNS). FGF signaling via FGFR1, one of the three FGFRs expressed in the CNS, stimulates proliferation of stem cells during prenatal and postnatal neurogenesis and participates in regulating cell-type ratios in many developing regions of the brain. Anomalies in FGFR1 signaling have been implicated in certain neuropsychiatric disorders. Fgfr1 expression has been shown, via in situ hybridization, to vary spatially and temporally throughout embryonic and postnatal development of the brain. However, in situ hybridization lacks sufficient resolution to identify which cell-types directly participate in FGF signaling. Furthermore, because antibodies raised against FGFR1 commonly cross-react with other members of the FGFR family, immunocytochemistry is not alone sufficient to accurately document Fgfr1 expression. Here, we elucidate the identity of Fgfr1 expressing cells in both the embryonic and perinatal mouse brain. METHODS: To do this, we utilized a tgFGFR1-EGFPGP338Gsat BAC line (tgFgfr1-EGFP+) obtained from the GENSAT project. The tgFgfr1-EGFP+ line expresses EGFP under the control of a Fgfr1 promoter, thereby causing cells endogenously expressing Fgfr1 to also present a positive GFP signal. Through simple immunostaining using GFP antibodies and cell-type specific antibodies, we were able to accurately determine the cell-type of Fgfr1 expressing cells. RESULTS: This technique revealed Fgfr1 expression in proliferative zones containing BLBP+ radial glial stem cells, such as the cortical and hippocampal ventricular zones, and cerebellar anlage of E14.5 mice, in addition to DCX+ neuroblasts. Furthermore, our data reveal Fgfr1 expression in proliferative zones containing BLBP+ cells of the anterior midline, hippocampus, cortex, hypothalamus, and cerebellum of P0.5 mice, in addition to the early-formed GFAP+ astrocytes of the anterior midline. DISCUSSION: Understanding when during development and where Fgfr1 is expressed is critical to improving our understanding of its function during neurodevelopment as well as in the mature CNS. This information may one day provide an avenue of discovery towards understanding the involvement of aberrant FGF signaling in neuropsychiatric disorders.
format Online
Article
Text
id pubmed-5493973
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher PeerJ Inc.
record_format MEDLINE/PubMed
spelling pubmed-54939732017-07-03 ­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system Collette, Jantzen C. Choubey, Lisha Smith, Karen Müller PeerJ Cell Biology BACKGROUND: Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in the development and function of multiple organs and organ systems, including the central nervous system (CNS). FGF signaling via FGFR1, one of the three FGFRs expressed in the CNS, stimulates proliferation of stem cells during prenatal and postnatal neurogenesis and participates in regulating cell-type ratios in many developing regions of the brain. Anomalies in FGFR1 signaling have been implicated in certain neuropsychiatric disorders. Fgfr1 expression has been shown, via in situ hybridization, to vary spatially and temporally throughout embryonic and postnatal development of the brain. However, in situ hybridization lacks sufficient resolution to identify which cell-types directly participate in FGF signaling. Furthermore, because antibodies raised against FGFR1 commonly cross-react with other members of the FGFR family, immunocytochemistry is not alone sufficient to accurately document Fgfr1 expression. Here, we elucidate the identity of Fgfr1 expressing cells in both the embryonic and perinatal mouse brain. METHODS: To do this, we utilized a tgFGFR1-EGFPGP338Gsat BAC line (tgFgfr1-EGFP+) obtained from the GENSAT project. The tgFgfr1-EGFP+ line expresses EGFP under the control of a Fgfr1 promoter, thereby causing cells endogenously expressing Fgfr1 to also present a positive GFP signal. Through simple immunostaining using GFP antibodies and cell-type specific antibodies, we were able to accurately determine the cell-type of Fgfr1 expressing cells. RESULTS: This technique revealed Fgfr1 expression in proliferative zones containing BLBP+ radial glial stem cells, such as the cortical and hippocampal ventricular zones, and cerebellar anlage of E14.5 mice, in addition to DCX+ neuroblasts. Furthermore, our data reveal Fgfr1 expression in proliferative zones containing BLBP+ cells of the anterior midline, hippocampus, cortex, hypothalamus, and cerebellum of P0.5 mice, in addition to the early-formed GFAP+ astrocytes of the anterior midline. DISCUSSION: Understanding when during development and where Fgfr1 is expressed is critical to improving our understanding of its function during neurodevelopment as well as in the mature CNS. This information may one day provide an avenue of discovery towards understanding the involvement of aberrant FGF signaling in neuropsychiatric disorders. PeerJ Inc. 2017-06-29 /pmc/articles/PMC5493973/ /pubmed/28674667 http://dx.doi.org/10.7717/peerj.3519 Text en ©2017 Collette et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Cell Biology
Collette, Jantzen C.
Choubey, Lisha
Smith, Karen Müller
­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system
title ­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system
title_full ­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system
title_fullStr ­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system
title_full_unstemmed ­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system
title_short ­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system
title_sort ­glial and stem cell expression of murine fibroblast growth factor receptor 1 in the embryonic and perinatal nervous system
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493973/
https://www.ncbi.nlm.nih.gov/pubmed/28674667
http://dx.doi.org/10.7717/peerj.3519
work_keys_str_mv AT collettejantzenc glialandstemcellexpressionofmurinefibroblastgrowthfactorreceptor1intheembryonicandperinatalnervoussystem
AT choubeylisha glialandstemcellexpressionofmurinefibroblastgrowthfactorreceptor1intheembryonicandperinatalnervoussystem
AT smithkarenmuller glialandstemcellexpressionofmurinefibroblastgrowthfactorreceptor1intheembryonicandperinatalnervoussystem