Negative Regulation of mTOR Signaling Restricts Cell Proliferation in the Floor Plate

Abstract

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.

Vitamin E Deficiency Disrupts Gene Expression Networks during Zebrafish Development

“…Importantly, we showed that glucose injections at 24 hpf rescued ~70% of E– embryos [ 11 ], providing a clue that earlier intervention may alter transcriptional responses and fully rescue E– animals through remediation of glycolysis. Importantly, vertebrate neurogenesis formation requires mTOR signaling [ 41 , 42 ] and mTOR is expressed in the zebrafish trunk and brain at 24 hpf [ 43 ].…”

Sox14 is essential for initiation of interneuron differentiation in the chick spinal cord

“…For tissue analyses, the harvested embryos were fixed with 4% paraformaldehyde for 90 min, and were replaced with 15% (w/v) sucrose overnight with rotating incubation. These embryos were In situ hybridisation and TUNEL assays were performed as previously described [6,38,39].…”

“…These embryos were embedded in OCT compound (Sakura) and cryosectioned to a thickness of 12 µm using a Polar cryostat (Sakura Finetek). The following antibodies were used in this study: Sox2 (rabbit; Millipore, #5603), In situ hybridisation and TUNEL assays were performed as previously described [6,38,39].…”

“…The ventral neural tube is consequently divided into six regions: p0-p2, motor neuron progenitor region (pMN), p3, and the FP, along the intermediate region to the ventral, whose assignment is dependent on the concentration of Shh. The cells proliferate to specific numbers in a region-specific manner [5,6].…”

Identification of genes related to intramuscular fat independent of backfat thickness in Duroc pigs using single‐step genome‐wide association

“…SSC1: 159538854 was found to be an intron variant of the Ring finger protein 152 ( RNF152 ) gene, which has been identified as a negative regulation factor of mTOR signaling (Deng et al . 2015; Kadoya & Sasai 2019). The mTOR pathway is involved in cell metabolism, survival and proliferation by regulating anabolic processes, including protein, lipid and nucleotide synthesis (Gangloff et al .…”