Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor Plate
The neural tube is composed of a number of neural progenitors and postmitotic neurons distributed in a quantitatively and spatially precise manner. The floor plate, located in the ventral-most region of the neural tube, has a lot of unique characteristics, including a low cell proliferation rate. Th...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-09-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2019.01022/full |
| _version_ | 1828393882560233472 |
|---|---|
| author | Minori Kadoya Noriaki Sasai |
| author_facet | Minori Kadoya Noriaki Sasai |
| author_sort | Minori Kadoya |
| collection | DOAJ |
| description | The neural tube is composed of a number of neural progenitors and postmitotic neurons distributed in a quantitatively and spatially precise manner. The floor plate, located in the ventral-most region of the neural tube, has a lot of unique characteristics, including a low cell proliferation rate. The mechanisms by which this region-specific proliferation rate is regulated remain elusive. Here we show that the activity of the mTOR signaling pathway, which regulates the proliferation of the neural progenitor cells, is significantly lower in the floor plate than in other domains of the embryonic neural tube. We identified the forkhead-type transcription factor FoxA2 as a negative regulator of mTOR signaling in the floor plate, and showed that FoxA2 transcriptionally induces the expression of the E3 ubiquitin ligase RNF152, which together with its substrate RagA, regulates cell proliferation via the mTOR pathway. Silencing of RNF152 led to the aberrant upregulation of the mTOR signal and aberrant cell division in the floor plate. Taken together, the present findings suggest that floor plate cell number is controlled by the negative regulation of mTOR signaling through the activity of FoxA2 and its downstream effector RNF152. |
| first_indexed | 2024-12-10T07:46:22Z |
| format | Article |
| id | doaj.art-d14544057f81477eb1be350e0eca873a |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-10T07:46:22Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-d14544057f81477eb1be350e0eca873a2022-12-22T01:57:11ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-09-011310.3389/fnins.2019.01022475239Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor PlateMinori KadoyaNoriaki SasaiThe neural tube is composed of a number of neural progenitors and postmitotic neurons distributed in a quantitatively and spatially precise manner. The floor plate, located in the ventral-most region of the neural tube, has a lot of unique characteristics, including a low cell proliferation rate. The mechanisms by which this region-specific proliferation rate is regulated remain elusive. Here we show that the activity of the mTOR signaling pathway, which regulates the proliferation of the neural progenitor cells, is significantly lower in the floor plate than in other domains of the embryonic neural tube. We identified the forkhead-type transcription factor FoxA2 as a negative regulator of mTOR signaling in the floor plate, and showed that FoxA2 transcriptionally induces the expression of the E3 ubiquitin ligase RNF152, which together with its substrate RagA, regulates cell proliferation via the mTOR pathway. Silencing of RNF152 led to the aberrant upregulation of the mTOR signal and aberrant cell division in the floor plate. Taken together, the present findings suggest that floor plate cell number is controlled by the negative regulation of mTOR signaling through the activity of FoxA2 and its downstream effector RNF152.https://www.frontiersin.org/article/10.3389/fnins.2019.01022/fullchickneural tubefloor platemTORcell proliferation |
| spellingShingle | Minori Kadoya Noriaki Sasai Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor Plate Frontiers in Neuroscience chick neural tube floor plate mTOR cell proliferation |
| title | Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor Plate |
| title_full | Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor Plate |
| title_fullStr | Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor Plate |
| title_full_unstemmed | Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor Plate |
| title_short | Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor Plate |
| title_sort | negative regulation of mtor signaling restricts cell proliferation in the floor plate |
| topic | chick neural tube floor plate mTOR cell proliferation |
| url | https://www.frontiersin.org/article/10.3389/fnins.2019.01022/full |
| work_keys_str_mv | AT minorikadoya negativeregulationofmtorsignalingrestrictscellproliferationinthefloorplate AT noriakisasai negativeregulationofmtorsignalingrestrictscellproliferationinthefloorplate |