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| Open AccessComplete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster
The cluster miR-17~92 modulates the expression of genes networks and signalling pathways to ensure proper Sry expression timing and subsequent testis differentiation, an unexpected role for miRNAs in the early steps of mammalian sex determination.
- Alicia Hurtado
- , Irene Mota-Gómez
- & Francisco J. Barrionuevo
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Article
| Open AccessEpiallelic variation of non-coding RNA genes and their phenotypic consequences
This study uncovers abundant DNA methylation variations of non-coding RNA genes in the natural Arabidopsis population and shows the importance of epigenetic variations in plant phenotypic plasticity and diversity.
- Jie Liu
- & Xuehua Zhong
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Article
| Open AccessThe dynamic genetic determinants of increased transcriptional divergence in spermatids
Here the authors show that genetic changes between species often alter gene expression in a cell type-specific manner. Most of this variability is driven by locally functioning cis-acting variation, and this contributes to the speed at which cell types accumulate expression changes.
- Jasper Panten
- , Tobias Heinen
- & Duncan T. Odom
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| Open AccessUnraveling the genetic architecture of congenital vertebral malformation with reference to the developing spine
Congenital vertebral malformation has a complex genetic architecture that isn’t fully understood. Here, the authors explore the genetic architecture of congenital vertebral malformation through case-control rare variant genetic analyses and embryonic transcriptome analyses of the developing spine.
- Sen Zhao
- , Hengqiang Zhao
- & Nan Wu
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Article
| Open AccessMADS1-regulated lemma and awn development benefits barley yield
HvMADS1 in barley positively regulates awn length and lemma width by promoting cell proliferation through direct action on the expression of HvSHI and HvDL. In wheat, MADS1 conservatively regulates awn length.
- Yueya Zhang
- , Chaoqun Shen
- & Dabing Zhang
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| Open AccessA distant global control region is essential for normal expression of anterior HOXA genes during mouse and human craniofacial development
The authors discovered cluster of regulatory sequences that controls HOXA over large genomic distances and across topological domains. This cluster is required for normal craniofacial development in both humans and mice.
- Andrea Wilderman
- , Eva D’haene
- & Justin Cotney
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| Open AccessThe homeodomain transcriptional regulator DVE-1 directs a program for synapse elimination during circuit remodeling
Synapse elimination is a critical process in the maturation of brain circuitry. Here the authors identify a key transcriptional program in Caenorhabditis elegans that directs the elimination of juvenile synapses during developmental circuit rewiring.
- Kellianne D. Alexander
- , Shankar Ramachandran
- & Michael M. Francis
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Article
| Open AccessHofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes
Placental inflammation is sometimes associated with health outcomes later in life. Here, the authors find that expression of genes associated with the homeostatic function of Hofbauer cells, a placenta-specific macrophage, are associated with protection from adult cardiovascular and depressive disorders
- Eamon Fitzgerald
- , Mojun Shen
- & Michael J. Meaney
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Article
| Open AccessProlonging somatic cell proliferation through constitutive hox gene expression in C. elegans
Somatic cells in C. elegans stop dividing after completing their normal lineage at the end of development. Here, Heinze et al. show that constitutive expression of a hox gene prolongs proliferation beyond the restriction imposed by the cell lineage.
- Svenia D. Heinze
- , Simon Berger
- & Alex Hajnal
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| Open AccessA DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci
The mechanism of spatiotemporal gene regulation during animal development is a fundamental question in biology. Here the authors show that the DEAD-box helicase DDX-23 controls stem cell fate by driving the formation of NAB repressive transcriptional condensates.
- Akiko Doi
- , Gianmarco D. Suarez
- & H. Robert Horvitz
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| Open AccessActivator-blocker model of transcriptional regulation by pioneer-like factors
How gene expression timing is regulated during development remains a key area of research. Here they show that zebrafish genome activators Pou5f3 and Nanog block each other’s activity on the enhancers of differentiation genes, preventing their premature expression.
- Aileen Julia Riesle
- , Meijiang Gao
- & Daria Onichtchouk
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Article
| Open AccessNacα protects the larval fat body from cell death by maintaining cellular proteostasis in Drosophila
Protein homeostasis is crucial for maintaining cellular homeostasis. Here, the authors show that proteotoxic stress caused by Nacalpha mutants specifically and progressively induces cell death in the apoptosis-resistant Drosophila larval fat body.
- Takayuki Yamada
- , Yuto Yoshinari
- & Takashi Nishimura
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Article
| Open AccessDNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood
Here the authors identify an association between methylation of the suppressor of cytokine signaling 3 (SOCS3) and height in children from India, Gambia and the UK.
- Prachand Issarapu
- , Manisha Arumalla
- & Stephen Owens
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| Open AccessSYPL1 defines a vesicular pathway essential for sperm cytoplasmic droplet formation and male fertility
The cytoplasmic droplet is an elusive structure of mammalian sperm. Here, the authors uncover a key gene that defines a vesicular pathway essential for cytoplasmic droplet formation and male fertility.
- Jiali Liu
- , Louis Hermo
- & Chen Chen
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Article
| Open AccessMaternal TDP-43 interacts with RNA Pol II and regulates zygotic genome activation
Zygotic genome activation is crucial for mammalian embryonic development. Here, the authors find that TDP-43 is indispensable for mouse embryonic development and mediates zygotic genome activation through Pol II configuration.
- Xiaoqing Nie
- , Qianhua Xu
- & Lei Li
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Article
| Open AccessDeficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. Here, using genetic data for 1.52 million individuals, the authors identify 25 genes with protein-altering variants exhibiting a strong deficit of homozygosity, suggesting they are essential for successful early development.
- Asmundur Oddsson
- , Patrick Sulem
- & Daniel F. Gudbjartsson
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| Open AccessBase editing-mediated one-step inactivation of the Dnmt gene family reveals critical roles of DNA methylation during mouse gastrulation
The role of DNA methylation in early embryo development has been difficult to determine due to the functional redundancy of DNA methyltransferases. Here they develop an efficient base editing system that enables one-step generation of Dnmt-null embryos and show that DNA methylation-related miRNA suppression may be involved in gastrulation.
- Qing Li
- , Jiansen Lu
- & Jinsong Li
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Article
| Open AccessBroad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility
Testis-specific serine/threonine kinases have been associated with male infertility, but the mechanism for this connection is unclear. Here they identify a Drosophila homolog, dTSSK, which is essential for male fertility in fruit flies and has functionally conserved catalytic activity with human TSSKs.
- Xuedi Zhang
- , Ju Peng
- & Guanjun Gao
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| Open AccessA DBHS family member regulates male determination in the filariasis vector Armigeres subalbatus
The Armigeres subalbatus sex-determining locus, M, maps to the 3rd chromosome, but its identity was unknown. Here they identify a sex-specific gene, AsuMf, that is essential for male development and show that it is a novel male-determining factor derived from duplication and neofunctionalization of a conserved DBHS family member.
- Peiwen Liu
- , Wenqiang Yang
- & Xiao-Guang Chen
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Article
| Open AccessCopy number variation in tRNA isodecoder genes impairs mammalian development and balanced translation
Enigmatically tRNA genes exist in several hundred copies in mammalian genomes. Here the authors find a precipitous failure of development and increased amino acid misincorporation upon systematic elimination of tRNA-Phe genes in mice using CRISPR.
- Laetitia A. Hughes
- , Danielle L. Rudler
- & Aleksandra Filipovska
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| Open AccessTranscriptomics of Hirschsprung disease patient-derived enteric neural crest cells reveals a role for oxidative phosphorylation
Hirschsprung disease is caused by defects in enteric neural crest cell. Here, using induced pluripotent stem cell-based models of Hirschsprung and single-cell transcriptomic analysis the authors define various factors associated with Hirschsprung pathogenesis.
- Zhixin Li
- , Kathy Nga-Chu Lui
- & Elly Sau-Wai Ngan
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| Open AccessFOXI3 pathogenic variants cause one form of craniofacial microsomia
Most cases of craniofacial microsomia are sporadic but familial cases have been reported. Here the authors report that variants in FOXI3 can cause a small fraction of cases with different modes of inheritance including autosomal dominant with reduced penetrance.
- Ke Mao
- , Christelle Borel
- & Stylianos E. Antonarakis
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| Open AccessVariations in the poly-histidine repeat motif of HOXA1 contribute to bicuspid aortic valve in mouse and zebrafish
Bicuspid aortic valve (BAV) is the most common cardiac defect and although highly heritable, few causal mutations have been identified. Here, the authors identify variants in the poly-histidine repeat motif of HOXA1 and show that its disruption leads to BAV in mice.
- Gaëlle Odelin
- , Adèle Faucherre
- & Stéphane Zaffran
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| Open AccessDefects in placental syncytiotrophoblast cells are a common cause of developmental heart disease
Placental dysfunction can affect heart development, but the prevalence of this causality has not been well established. Here, the authors use mouse genetic tools to show that the placenta may constitute a significant source of congenital heart defects.
- Bethany N. Radford
- , Xiang Zhao
- & Myriam Hemberger
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Article
| Open AccessTiller Number1 encodes an ankyrin repeat protein that controls tillering in bread wheat
Tiller number is an important agronomic trait of wheat. Here, the authors clone a positive regulator of wheat tiller number and show that the encoded ankyrin repeat protein can promote tiller bud outgrowth through inhibiting ABA biosynthesis and signaling.
- Chunhao Dong
- , Lichao Zhang
- & Xu Liu
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| Open AccessJNK signaling in pioneer neurons organizes ventral nerve cord architecture in Drosophila embryos
The shape and size of the mature central nervous system is highly regular, implying precise architectural rules. The authors show that alterations in JNK signaling in selected neurons impact the overall 3-dimensional organization of the Drosophila ventral nerve cord in a cell non-autonomous fashion.
- Katerina Karkali
- , Timothy E. Saunders
- & Enrique Martín-Blanco
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Article
| Open AccessThe function and evolution of a genetic switch controlling sexually dimorphic eye differentiation in honeybees
Sexual dimorphism results in widely diverse animal forms, but sexual determination is generally attributed to a single gene in animal models. Here they find that the glu gene regulates sexual dimorphism of honeybee eyes, demonstrating diversification of genetic programs for dimorphism.
- Oksana Netschitailo
- , Yidong Wang
- & Martin Beye
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Article
| Open AccessWnt/β-catenin signalling is required for pole-specific chromatin remodeling during planarian regeneration
Any planarian fragment regenerates the missing head and tail in the proper end. Early activation of the Wnt/β-catenin signaling pathway changes the chromatin accessibility of the cells of the posterior-facing wound to regenerate a tail.
- Eudald Pascual-Carreras
- , Marta Marín-Barba
- & Teresa Adell
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| Open AccessSingle-cell transcriptomic analysis identifies murine heart molecular features at embryonic and neonatal stages
A detailed multi-staged single cell atlas of heart development could improve our understanding of cell type diversification during cardiac development. Here, the authors generated a large dataset with cells from embryonic and neonatal hearts to identify the stage and chamber specific features in heart development.
- Wei Feng
- , Abha Bais
- & Guang Li
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| Open AccessNr6a1 controls Hox expression dynamics and is a master regulator of vertebrate trunk development
The authors identify Nuclear receptor subfamily 6 group A member 1 (Nr6a1) as a master regulator of elongation, segmentation, patterning and lineage allocation specifically within the trunk region of the mouse, acting downstream of the major signals known to control vertebral column formation.
- Yi-Cheng Chang
- , Jan Manent
- & Edwina McGlinn
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| Open AccessmTORC1 signaling facilitates differential stem cell differentiation to shape the developing murine lung and is associated with mitochondrial capacity
Lung branching requires differentiation of progenitor cells to be coordinated with morphogenetic events. Zhang et al. find that loss of mTORC1 signaling in the distal SOX9+ lung progenitors reduces mitochondrial capacity and ATP production, thus disrupting the formation of the conducting airways without affecting the development of the gas exchange unit.
- Kuan Zhang
- , Erica Yao
- & Pao-Tien Chuang
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Article
| Open AccessDevelopmental disruption and restoration of brain synaptome architecture in the murine Pax6 neurodevelopmental disease model
Brain-wide mapping of synapse molecular composition in Pax6 mutant mice shows remodelling and restoration of synaptome architecture during development, a possible means of conferring resilience to genetic disorders.
- Laura Tomas-Roca
- , Zhen Qiu
- & Seth G. N. Grant
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| Open AccessTranslation and natural selection of micropeptides from long non-canonical RNAs
Translation of 100 to 300 micropeptides from small ORFs within lncRNA was detected by Ribosomal Profiling in Drosophila embryos. These translated small ORFs showed natural selection conserving micropeptide sequence and function.
- Pedro Patraquim
- , Emile G. Magny
- & Juan Pablo Couso
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| Open AccessBrain milieu induces early microglial maturation through the BAX-Notch axis
The mechanisms by which the brain milieu confers microglial development are not clear. Here, the authors show that the BAX-CaMKII-CREB-Notch signaling axis triggered by the neuronal milieu plays a role in early microglia maturation.
- Fangying Zhao
- , Jiangyong He
- & Li Li
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Article
| Open AccessIntrinsic myocardial defects underlie an Rbfox-deficient zebrafish model of hypoplastic left heart syndrome
The developmental mechanisms responsible for the structural defects observed in hypoplastic left heart syndrome remain controversial. Using rbfox-deficient zebrafish, the authors implicate impaired cardiac function as a primary driver of disease.
- Mengmeng Huang
- , Alexander A. Akerberg
- & Caroline E. Burns
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| Open AccessA Dilp8-dependent time window ensures tissue size adjustment in Drosophila
Mechanisms ensuring developmental precision are poorly understood. Here Blanco-Obregon et al. report reciprocal feedback between Dilp8 and Ecdysone, two hormones required during a precise time window of Drosophila development for organ size adjustment.
- D. Blanco-Obregon
- , K. El Marzkioui
- & L. Boulan
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Article
| Open AccessMettl3-mediated mRNA m6A modification controls postnatal liver development by modulating the transcription factor Hnf4a
m6A is the most abundant RNA modification of eukaryotic mRNAs and is involved in various physiological and pathological processes. Here the authors show a role for Mettl3-mediated RNA m6A modification in postnatal liver development by regulating the Hnf4a-centered transcriptional network
- Yan Xu
- , Zhuowei Zhou
- & Qi Zhang
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| Open AccessMyriapod genomes reveal ancestral horizontal gene transfer and hormonal gene loss in millipedes
Myriapods play an important ecological role in soil and forest ecosystems. Here the authors analyse nine myriapod genomes, showing rapid evolution of distinct genomic pathways in centipede and millipede lineages, shaped by differing ecological pressures.
- Wai Lok So
- , Wenyan Nong
- & Jerome H. L. Hui
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| Open AccessDifferential regulation of alternative promoters emerges from unified kinetics of enhancer-promoter interaction
Alternative promoters differ in their expression patterns, whose mechanisms are not well understood. Here the authors show that alternative promoters of a Drosophila embryonic gene hunchback are regulated by different action modes of two enhancers.
- Jingyao Wang
- , Shihe Zhang
- & Heng Xu
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Article
| Open AccessPossible stochastic sex determination in Bursaphelenchus nematodes
In most species, sex is determined by genetic or environmental factors. Here, the authors present evidence that sex determination in Bursaphelenchus nematodes is instead likely to be regulated by a random, epigenetic mechanism.
- Ryoji Shinya
- , Simo Sun
- & Paul W. Sternberg
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Article
| Open AccessMultilayered regulations of alternative splicing, NMD, and protein stability control temporal induction and tissue-specific expression of TRIM46 during axon formation
The genetic control underlying axon formation in neurons is unknown. Here, the authors report that neural-specific induction of TRIM46, one of the earliest axonal markers, is regulated by alternative splicing, NMD, and protein stability controls.
- John K. Vuong
- , Volkan Ergin
- & Sika Zheng
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Article
| Open AccessSex-linked deubiquitinase establishes uniparental transmission of chloroplast DNA
Most sexual organisms ensure that organelles are inherited from a single parent. Here, the authors describe OTU2p, a Chlamydomonas deubiquitinase that drives uniparental organelle inheritance without gametic dimorphism by preventing proteasome-mediated degradation exclusively in gametes of the plus mating type.
- Sunjoo Joo
- , Thamali Kariyawasam
- & Jae-Hyeok Lee
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Article
| Open AccessPlacental genomics mediates genetic associations with complex health traits and disease
The impact of placental transcriptomics on fetal traits throughout development is not well understood. Here, the authors apply distal-SNP-enriched transcriptome-wide association studies to detect genetic contributions, mediated through fetal placental genomics, to developmental programming of complex traits across the life course.
- Arjun Bhattacharya
- , Anastasia N. Freedman
- & Hudson P. Santos Jr
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Article
| Open AccessIdentification of a modular super-enhancer in murine retinal development
Super-enhancers are regions of genomic DNA comprised of multiple putative enhancers that contribute to dynamic gene expression patterns during development. Here the authors identify a modular super-enhancer in murine retinal development and show that distinct modules are responsible for retinal progenitor cell proliferation during early and bipolar neuron genesis during late retinal development.
- Victoria Honnell
- , Jackie L. Norrie
- & Michael A. Dyer
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Article
| Open AccessDynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis
The domestic chicken Gallus gallus domesticus is a classic model for the study of folliculogenesis. Here the authors integrate multi-omics analyses characterizing the dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis.
- Diyan Li
- , Chunyou Ning
- & Mingzhou Li
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Article
| Open AccessCell-specific alterations in Pitx1 regulatory landscape activation caused by the loss of a single enhancer
Developmental genes are frequently controlled by multiple enhancers sharing similar specificities, so deletions of such regulatory elements often fail to reveal their full function. Here the authors use the Pitx1 testbed locus to characterize the regulatory and cellular identity alterations following the deletion in vivo of one of its enhancers.
- Raquel Rouco
- , Olimpia Bompadre
- & Guillaume Andrey
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Article
| Open AccessA somatic proteoglycan controls Notch-directed germ cell fate
Notch receptor GLP-1 is required for maintaining germ cells in the C. elegans germline. Here the authors show that syndecan-1, a somatic transmembrane proteoglycan regulates expression of glp-1 and germ cell mitosis in C. elegans, by promoting calcium-dependent binding of APTF-2 to the glp-1 promoter.
- Sandeep Gopal
- , Aqilah Amran
- & Roger Pocock
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Article
| Open AccessPegasus, a small extracellular peptide enhancing short-range diffusion of Wingless
Short open reading frames (smORFs) of less than 100 codons exist in the thousands in metazoan genomes, mostly with yet unknown functions. Here the authors show how a smORF conserved from flies to vertebrates produces a secreted peptide that enhances the diffusion of the cell signalling protein Wingless.
- Emile G. Magny
- , Ana Isabel Platero
- & Juan Pablo Couso
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Article
| Open AccessA PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling
Mutations in daf-2/insulin/IGF-1 receptor impair the growth and reproduction of C. elegans but conversely enhance immunity and lifespan. Here, the authors show that a missense mutation in the gene retains the effects on lifespan and immunity and improves motility.
- Hae-Eun H. Park
- , Wooseon Hwang
- & Seung-Jae V. Lee