Disruption of the suprachiasmatic nucleus in fibroblast growth factor signaling-deficient mice
Fibroblast growth factor (Fgf) 8 is essential for the development of multiple brain regions. Previous studies from our laboratory showed that reduced Fgf8 signaling led to the developmental alterations of neuroendocrine nuclei that originated within the diencephalon, including the paraventricular (...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fendo.2016.00011/full |
| _version_ | 1811253732433723392 |
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| author | Ann Virginia Miller Scott eKavanaugh Pei-San eTsai |
| author_facet | Ann Virginia Miller Scott eKavanaugh Pei-San eTsai |
| author_sort | Ann Virginia Miller |
| collection | DOAJ |
| description | Fibroblast growth factor (Fgf) 8 is essential for the development of multiple brain regions. Previous studies from our laboratory showed that reduced Fgf8 signaling led to the developmental alterations of neuroendocrine nuclei that originated within the diencephalon, including the paraventricular (PVN) and supraoptic (SON) nuclei. To further understand the role of Fgf8 in the development of other hypothalamic nuclei, we examined if Fgf8 and its cognate receptor, Fgfr1, also impact the integrity of the suprachiasmatic nuclei (SCN). The SCN control an organism’s circadian rhythm and contain vasoactive intestinal peptide (VIP)-producing neurons as the main input neurons. Mice hypomorphic for Fgf8, Fgfr1, or both were examined for their SCN volume and the number of VIP neurons on postnatal day (PN) 0; adult hypomorphic mice were further examined for SCN function by quantifying SCN neuronal activation using cFos as a marker. On PN0, mice homozygous for Fgf8 hypomorphy displayed the most severe reduction of the SCN volume and VIP neurons. Those heterozygous for Fgf8 hypomorphy alone or Fgf8 combined with Fgfr1 hypomorphy, called double heterozygotes (DH), showed normal SCN volume but significantly reduced VIP neurons, albeit less severely than the homozygotes. Adult wildtype (WT), heterozygous Fgf8 hypomorphs (F8 Het), and DH mice were also examined for SCN cFos activation at three time points: 1 (morning), 6 (afternoon), and 11 (evening) hours after light onset. In F8 Het mice, a significant change in the pattern of cFos immunostaining that may reflect delayed morning SCN activation was observed. Overall, our studies provide evidence supporting that deficiencies in Fgf8 not only impact the structural integrity of the SCN, but also the pattern of SCN activation in response to light. |
| first_indexed | 2024-04-12T16:56:32Z |
| format | Article |
| id | doaj.art-443d4cefa80442588737b1540014f20b |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T16:56:32Z |
| publishDate | 2016-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-443d4cefa80442588737b1540014f20b2022-12-22T03:24:13ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922016-02-01710.3389/fendo.2016.00011177267Disruption of the suprachiasmatic nucleus in fibroblast growth factor signaling-deficient miceAnn Virginia Miller0Scott eKavanaugh1Pei-San eTsai2University of ColoradoUniversity of ColoradoUniversity of ColoradoFibroblast growth factor (Fgf) 8 is essential for the development of multiple brain regions. Previous studies from our laboratory showed that reduced Fgf8 signaling led to the developmental alterations of neuroendocrine nuclei that originated within the diencephalon, including the paraventricular (PVN) and supraoptic (SON) nuclei. To further understand the role of Fgf8 in the development of other hypothalamic nuclei, we examined if Fgf8 and its cognate receptor, Fgfr1, also impact the integrity of the suprachiasmatic nuclei (SCN). The SCN control an organism’s circadian rhythm and contain vasoactive intestinal peptide (VIP)-producing neurons as the main input neurons. Mice hypomorphic for Fgf8, Fgfr1, or both were examined for their SCN volume and the number of VIP neurons on postnatal day (PN) 0; adult hypomorphic mice were further examined for SCN function by quantifying SCN neuronal activation using cFos as a marker. On PN0, mice homozygous for Fgf8 hypomorphy displayed the most severe reduction of the SCN volume and VIP neurons. Those heterozygous for Fgf8 hypomorphy alone or Fgf8 combined with Fgfr1 hypomorphy, called double heterozygotes (DH), showed normal SCN volume but significantly reduced VIP neurons, albeit less severely than the homozygotes. Adult wildtype (WT), heterozygous Fgf8 hypomorphs (F8 Het), and DH mice were also examined for SCN cFos activation at three time points: 1 (morning), 6 (afternoon), and 11 (evening) hours after light onset. In F8 Het mice, a significant change in the pattern of cFos immunostaining that may reflect delayed morning SCN activation was observed. Overall, our studies provide evidence supporting that deficiencies in Fgf8 not only impact the structural integrity of the SCN, but also the pattern of SCN activation in response to light.http://journal.frontiersin.org/Journal/10.3389/fendo.2016.00011/fulldevelopmentVIPFGFR1cfosFgf8SCN |
| spellingShingle | Ann Virginia Miller Scott eKavanaugh Pei-San eTsai Disruption of the suprachiasmatic nucleus in fibroblast growth factor signaling-deficient mice Frontiers in Endocrinology development VIP FGFR1 cfos Fgf8 SCN |
| title | Disruption of the suprachiasmatic nucleus in fibroblast growth factor signaling-deficient mice |
| title_full | Disruption of the suprachiasmatic nucleus in fibroblast growth factor signaling-deficient mice |
| title_fullStr | Disruption of the suprachiasmatic nucleus in fibroblast growth factor signaling-deficient mice |
| title_full_unstemmed | Disruption of the suprachiasmatic nucleus in fibroblast growth factor signaling-deficient mice |
| title_short | Disruption of the suprachiasmatic nucleus in fibroblast growth factor signaling-deficient mice |
| title_sort | disruption of the suprachiasmatic nucleus in fibroblast growth factor signaling deficient mice |
| topic | development VIP FGFR1 cfos Fgf8 SCN |
| url | http://journal.frontiersin.org/Journal/10.3389/fendo.2016.00011/full |
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