Biology subjects

Cinnamon, Y.

Publications and source records attributed to Cinnamon, Y..

4 recordsLinked to original sources

bioRxiv2022

IGF2BP2 is Induced by Stress in the Heart and Mediates Dilated Cardiomyopathy

The IGF2BP family of RNA binding proteins consists of three paralogs that regulate intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. Previous studies indicated that IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodelling and returns to normal levels in recovering hearts. These results raise the possibility that IGF2BP2 might play an adaptive role during cardiac stress and recovery. Using a conditional, inducible transgenic mouse line, we found that enhanced expression of an IGF2BP2 transgene in newborn or adult hearts leads to dilated cardiomyopathy (DCM) and death within 3-4 weeks. Downregulation of the transgene after 2 weeks, however, rescues these mice, with complete recovery by 12 weeks. Hearts overexpressing IGF2BP2 downregulate sarcomeric and mitochondrial proteins and have fragmented mitochondria and elongated, thinner sarcomeres. Consistent with these results, IGF2BP2 is upregulated in patients with DCM or after myocardial infarction. These results suggest that IGF2BP2 may be an attractive target for therapeutic intervention in DCM.

cell biology↗

bioRxiv2022

HREM, RNAseq and cell-cycle analyses reveal the role of the G2/M-regulatory protein, Wee1, on the survivability of chicken embryos during diapause.

Avian blastoderm can enter into diapause when kept at low temperatures, and successfully resume development (SRD) when re-incubated in body-temperature. These abilities, which are largely affected by the temperature and duration of the diapause, are poorly understood at the cellular and molecular level. To determine how temperature affects embryonic morphology during diapause, High-Resolution Episcopic Microscopy (HREM) analysis was utilized. While blastoderms diapausing at 12{degrees}C for 28 days presented typical cytoarchitecture, similar to non-diapaused embryos, at 18{degrees}C much thicker blastoderms with higher cell-number were observed. RNAseq was conducted to discover the genes underlying these phenotypes, revealing differentially-expressed cell-cycle regulatory genes. Amongst them, Wee1, a negative-regulator of G2/M transition, was highly expressed at 12{degrees}C compared to 18{degrees}C. This finding suggested that cells at 12{degrees}C are arrested at the G2/M phase, as supported by bromodeoxyuridine incorporation (BrdU) assay and phosho-histone-H3 (pH3) immuno-staining. Inhibition of Wee1 during diapause at 12{degrees}C resulted in cell-cycle progression beyond the G2/M and augmented tissue volume, resembling the morphology of 18{degrees}C-diapaused embryos. These findings suggest that diapause at low temperatures leads to Wee1 upregulation which arrests the cell-cycle at the G2/M phase, promoting the perseverance of embryonic cytoarchitecture and future SRD. In contrast, Wee1 is not up-regulated during diapause at higher temperature, leading to continuous proliferation and maladaptive morphology associated with poor survivability. Combining HREM-based analysis with RNAseq and molecular manipulations, we present a novel mechanism that regulates the ability of diapaused-avian embryos to maintain their cytoarchitecture via cell-cycle arrest, which enables their SRD.

evolutionary biology↗

bioRxiv2021

How do avian embryos resume development following diapause? A new role for TGF-β in regulating pluripotency-related genes

Avian embryos can halt their development for long periods at low temperature in a process called diapause and successfully resume development when reincubated at maternal body temperature. Successful resumption of development depends on different factors, including temperature. We have recently shown that embryos that enter diapause at 18 {degrees}C present a significant reduction in their ability to develop normally when put back into incubation, compared to embryos entering diapause at 12 {degrees}C. However, the mechanisms underlying these differences are unknown. To address this question, transcriptome analysis was performed to compare the effect of diapause temperature on gene expression, and to identify pathways involved in the process. Genetic comparison and pathway-enrichment analysis revealed that TGF-{beta} and pluripotency-related pathways are differentially regulated at the two temperatures, with higher expression at 12 {degrees}C compared to 18 {degrees}C. Investigating the involvement of the TGF-{beta} pathway revealed an essential role for BMP4 in regulating the expression of the transcription factors Nanog and Id2, which are known to regulate pluripotency and self-renewal in embryonic stem cells. BMP4 gain- and loss-of-function experiments in embryos in diapause at the different temperatures revealed the main role of BMP4 in enabling resumption of normal development following diapause. Collectively, these findings identify molecular regulators that facilitate embryos ability to undergo diapause at different temperatures and resume a normal developmental program.

developmental biology↗

bioRxiv2020

A subpopulation of spinocerebellar tract neurons regulates the stability of bipedal stepping

Peripheral and intraspinal feedback is required to shape and update the output of spinal networks that execute motor behavior. We report that lumbar dI2 spinal interneurons of the chick receive synaptic input from afferents and pre-motoneurons. They innervate contralateral premotor networks in the lumbar and brachial spinal cord and their ascending projections innervate the cerebellum. These findings suggest that dI2 neurons function as interneurons in local lumbar circuits and involved in lumbo-brachial coupling and that part of them deliver peripheral and intraspinal feedback to the cerebellum. Silencing of dI2 neurons leads to destabilized stepping in P8 hatchlings with occasional collapses, variable step-profiles and wide-base walking, suggesting that the dI2 neurons may contribute to stabilization of the bipedal gait.

neuroscience↗