Astrocyte Development and Function is FGF8 Signaling Dependent

Astrocyte Development and Function is FGF8 Signaling Dependent

Bibliographic Details
Main Author: Stewart, Courtney Elizabeth
Language:English
Published: Kent State University / OhioLINK 2019
Subjects:
Biomedical Research
Neurosciences
FGF8
Astrocytes
GFAP
Astrocyte Activation
Agenesis of the corpus callosum
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=kent1556290142104336
id ndltd-OhioLink-oai-etd.ohiolink.edu-kent1556290142104336
record_format oai_dc
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-kent15562901421043362021-08-03T07:10:49Z Astrocyte Development and Function is FGF8 Signaling Dependent Stewart, Courtney Elizabeth Biomedical Research Neurosciences FGF8 Astrocytes GFAP Astrocyte Activation Agenesis of the corpus callosum Brain development is dependent upon multiple ligand/receptor combinations within fibroblast growth factor (FGF) / fibroblast growth factor receptor (FGFR) signaling. FGFs are crucial for brain development as they regulate cell proliferation, specification, differentiation, migration and survival. Most FGF ligand actions during brain development are region-specific and many knockout studies have shown FGFs are involved in neural induction, brain symmetry, cortical, forebrain, midbrain and cerebellar development. Here, we showed that FGF8 signaling, which is known to provide trophic support for astrocytes during development, is also required for proper midline astrocyte development and function. Specifically, we showed that a <i>Fgf8</i> deficit delayed the acquisition of GFAP ultimately impairing the maturation of midline astrocytes, and subsequently resulting in agenesis of the corpus callosum (ACC). To our surprise, this delay in astrocyte maturation was transient, as adult <i>Fgf8</i> hypomorphic mice expressed midline astrocytic GFAP levels identical to their WT littermates indicating that astrocyte development in mice with FGF8 deficits normalized in adulthood. However, this did not rule out the possibility that perinatal <i>Fgf8</i> deficits may have permanent effects on astrocyte function, such as astrocyte activation. Therefore, we stressed <i>Fgf8</i> hypomorphic astrocytes with cuprizone (CPZ), a toxin which can target and activate corpus callosum specific astrocytes, and compared the astrocyte activation response between WT and <i>Fgf8</i><sup>+/neo</sup> hypomorphic mice. We found that a perinatal <i>Fgf8</i> deficit permanently impaired midline astrocytic function. Specifically, astrocytes within the cingulum region of the corpus callosum in adult <i>Fgf8</i><sup>+/neo</sup> CPZ-fed hypomorphic mice exhibited a delay in GFAP acquisition, and an altered astrocytic branching morphology. Furthermore, callosal cell populations within <i>Fgf8</i><sup>+/neo</sup> CPZ-fed hypomorphic mice exhibited an abnormal second messenger system profile when compared to WT CPZ-fed mice. Specifically, <i>Fgfr1</i> and <i>Stat3</i> mRNA increased in CPZ-fed <i>Fgf8</i><sup>+/neo</sup> hypomorphic mice. These studies demonstrate that, in addition to FGF8’s role as a source of astrocytic trophic support, FGF8 also plays an important role in GFAP acquisition, astrocyte maturation and astrocyte activation. Together, these studies have expanded our knowledge on, not only FGF8’s role in brain development, but also how FGF8 regulates astrocyte development and function. 2019-04-30 English text Kent State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=kent1556290142104336 http://rave.ohiolink.edu/etdc/view?acc_num=kent1556290142104336 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biomedical Research
Neurosciences
FGF8
Astrocytes
GFAP
Astrocyte Activation
Agenesis of the corpus callosum
spellingShingle Biomedical Research
Neurosciences
FGF8
Astrocytes
GFAP
Astrocyte Activation
Agenesis of the corpus callosum
Stewart, Courtney Elizabeth
Astrocyte Development and Function is FGF8 Signaling Dependent
author Stewart, Courtney Elizabeth
author_facet Stewart, Courtney Elizabeth
author_sort Stewart, Courtney Elizabeth
title Astrocyte Development and Function is FGF8 Signaling Dependent
title_short Astrocyte Development and Function is FGF8 Signaling Dependent
title_full Astrocyte Development and Function is FGF8 Signaling Dependent
title_fullStr Astrocyte Development and Function is FGF8 Signaling Dependent
title_full_unstemmed Astrocyte Development and Function is FGF8 Signaling Dependent
title_sort astrocyte development and function is fgf8 signaling dependent
publisher Kent State University / OhioLINK
publishDate 2019
url http://rave.ohiolink.edu/etdc/view?acc_num=kent1556290142104336
work_keys_str_mv AT stewartcourtneyelizabeth astrocytedevelopmentandfunctionisfgf8signalingdependent
_version_ 1719455464610070528

Similar Items