Role of mouse Wdr13 in placental growth; a genetic evidence for lifetime body weight determination by placenta during development

Singh, Vijay Pratap; Alex, Jomini Liza; Lakshmi, B. Jyothi; Sailasree, S Purnima; Raj, T. Avinash; Kumar, Satish

doi:10.1038/srep13371

Cited by 8 publications

(14 citation statements)

References 33 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, the glycogen content of the JZ decreases in late gestation as GCs are lysed, coinciding with expansion of the labyrinth compartment at this time ( 100 , 118 ). If so, this may contribute to abnormal development of the labyrinth in placentas with JZ defects ( 119 , 120 ).…”

Section: Placental Structures Linked To Embryonic Growthmentioning

confidence: 99%

Regulation of Placental Development and Its Impact on Fetal Growth—New Insights From Mouse Models

2018

View full text Add to dashboard Cite

The placenta is the chief regulator of nutrient supply to the growing embryo during gestation. As such, adequate placental function is instrumental for developmental progression throughout intrauterine development. One of the most common complications during pregnancy is insufficient growth of the fetus, a problem termed intrauterine growth restriction (IUGR) that is most frequently rooted in a malfunctional placenta. Together with conventional gene targeting approaches, recent advances in screening mouse mutants for placental defects, combined with the ability to rapidly induce mutations in vitro and in vivo by CRISPR-Cas9 technology, has provided new insights into the contribution of the genome to normal placental development. Most importantly, these data have demonstrated that far more genes are required for normal placentation than previously appreciated. Here, we provide a summary of common types of placental defects in established mouse mutants, which will help us gain a better understanding of the genes impacting on human placentation. Based on a recent mouse mutant screen, we then provide examples on how these data can be mined to identify novel molecular hubs that may be critical for placental development. Given the close association between placental defects and abnormal cardiovascular and brain development, these functional nodes may also shed light onto the etiology of birth defects that co-occur with placental malformations. Taken together, recent insights into the regulation of mouse placental development have opened up new avenues for research that will promote the study of human pregnancy conditions, notably those based on defects in placentation that underlie the most common pregnancy pathologies such as IUGR and pre-eclampsia.

show abstract

Section: Placental Structures Linked To Embryonic Growthmentioning

confidence: 99%

Regulation of Placental Development and Its Impact on Fetal Growth—New Insights From Mouse Models

2018

View full text Add to dashboard Cite

show abstract

“…WDR13 is a member of the WD-repeat protein family, conserved in vertebrates and expressed ubiquitously in many tissues [ 19 – 21 ]. A previous report from our laboratory showed that the absence of WDR13 led to enhanced pancreatic beta cell proliferation in mice [ 22 ] and the lack of this protein in a diabetic mouse model ( Leptin receptor mutant ), which has augmented JNK activity, showed reduced levels of AP1 target genes [ 23 ] and protection from inflammation.…”

Section: Introductionmentioning

confidence: 99%

WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice

2017

Self Cite

View full text Add to dashboard Cite

BackgroundWDR13 is a member of the WD repeat protein family and is expressed in several tissues of human and mice. Previous studies in our laboratory showed that the lack of this gene in mice resulted in mild obesity, hyperinsulinemia, enhanced beta cell proliferation and protection from inflammation. However, the molecular mechanism of WDR13 action is not well understood.MethodsIn the present study, we used AOM/DSS to induce colitis-mediated colorectal tumor after establishing expression of Wdr13 gene in colon. Further, we have used human colon cancer cell lines, HT29 and COLO205, and mouse primary embryonic fibroblast to understand the molecular mechanism of WDR13 action.ResultsWe observed that mice lacking Wdr13 gene have reduced number of tumors and are more susceptible to DSS-induced colon ulcers. We also show that WDR13 is a part of multi protein complex c-Jun/NCoR1/HDAC3 and it acts as a transcriptional activator of AP1 target genes in the presence of JNK signal. Consistent with in vitro data, we observed reduced expression of AP1 target genes in colon after AOM/DSS treatment in Wdr13 knockout mice as compared to that in wild type.ConclusionMice lacking Wdr13 gene showed reduced expression of AP1 target genes and protection from colitis-induced colorectal tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3118-7) contains supplementary material, which is available to authorized users.

show abstract

“…To elucidate its function, a gene-knockout mouse was generated in our laboratory. The absence of this gene in mice ( Wdr13 −/0 ) resulted in age-dependent mild obesity, pancreatic beta cell hyper-proliferation, subsequent hyper-insulinemia (Singh et al, 2012 ) and improvement of metabolic phenotype in Lepr (db/db) mice (Singh et al, 2015a ).…”

Section: Introductionmentioning

confidence: 99%

Implication of Genetic Deletion of Wdr13 in Mice: Mild Anxiety, Better Performance in Spatial Memory Task, with Upregulation of Multiple Synaptic Proteins

Mitra

Kumar

Tiwari

et al. 2016

Front. Mol. Neurosci.

Self Cite

View full text Add to dashboard Cite

WDR13 expresses from the X chromosome and has a highly conserved coding sequence. There have been multiple associations of WDR13 with memory. However, its detailed function in context of brain and behavior remains unknown. We characterized the behavioral phenotype of 2 month old male mice lacking the homolog of WDR13 gene (Wdr13−/0). Taking cue from analysis of its expression in the brain, we chose hippocampus for molecular studies to delineate its function. Wdr13−/0 mice spent less time in the central area of the open field test (OFT) and with the novel object in novel object recognition test (NOR) as compared to the wild-type. However, these mice didn't show any significant changes in total time spent in arms or in frequency of arm entries in elevated plus maze (EPM). In the absence of Wdr13, there was a significant upregulation of synaptic proteins, viz., SYN1, RAB3A, CAMK2A etc. accompanied with increased spine density of hippocampal CA1 neurons and better spatial memory in mice as measured by increased time spent in the target quadrant of Morris water maze (MWM) during probe test. Parallel study from our lab has established c-JUN, ER α/β, and HDAC 1,3,7 as interacting partners of WDR13. WDR13 represses transcription from AP1 (c-JUN responsive) and Estrogen Receptor Element (ERE) promoters. We hypothesized that absence of Wdr13 would result in de-regulated expression of a number of genes including multiple synaptic genes leading to the observed phenotype. Knocking down Wdr13 in Neuro2a cell lines led to increased transcripts of Camk2a and Nrxn2 consistent with in-vivo results. Summarily, our data provides functional evidence for the role of Wdr13 in brain.

show abstract

Role of mouse Wdr13 in placental growth; a genetic evidence for lifetime body weight determination by placenta during development

Cited by 8 publications

References 33 publications

Regulation of Placental Development and Its Impact on Fetal Growth—New Insights From Mouse Models

Regulation of Placental Development and Its Impact on Fetal Growth—New Insights From Mouse Models

WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice

Implication of Genetic Deletion of Wdr13 in Mice: Mild Anxiety, Better Performance in Spatial Memory Task, with Upregulation of Multiple Synaptic Proteins

Contact Info

Product

Resources

About