Placental labyrinth formation in mice requires endothelial FLRT2–UNC5B signaling

Tai-Nagara, Ikue; Yoshikawa, Yusuke; Numata, Naoko; Ando, Tomofumi; Okabe, Keisuke; Ieda, Masaki; Takakura, Nobuyuki; Nakagawa, Osamu; Zhou, Bin; Okabayashi, Koji; Suematsu, Makoto; Kitagawa, Yuko; Bastmeyer, Martin; Sato, Kohji; Klein, Rüdiger; Navankasattusas, Sutip; Li, Dean Y.; Yamagishi, Satoru; Kubota, Yoshiaki

doi:10.1242/dev.149757

Cited by 26 publications

(41 citation statements)

References 44 publications

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“…Several candidate genes are located within the SSC 7 QTL region (107-110 Mb) associated with VA and VH in Landrace: Fibronectin Leucine Rich Transmembrane protein 2 (FLRT2), Spermatogenesis Associated 7 (SPATA7), Transforming Growth Factor Beta 3 (TGFB3) and Interferon Regulatory Factor 2 Binding Protein Like (IRF2BPL). FLRT2 has been identified to be required for embryonic development in using mice [32][33][34][35][36]. In a GWAS study using commercial Large White and Landrace pigs, FLRT2 was proposed as a candidate gene for a QTL on SSC 7 (114.35-114.36 Mb) for number of piglets born alive [37], which further supports our hypothesis of VS traits being associated with farrowing performance.…”

Section: Genome-wide Association Analysissupporting

confidence: 69%

Genetic and genomic characterization of vulva size traits in Yorkshire and Landrace gilts

Corredor

Sanglard

Leach³

et al. 2020

BMC Genet

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Background: Reproductive performance is critical for efficient swine production. Recent results indicated that vulva size (VS) may be predictive of reproductive performance in sows. Study objectives were to estimate genetic parameters, identify genomic regions associated, and estimate genomic prediction accuracies (GPA) for VS traits. Results: Heritability estimates of VS traits, vulva area (VA), height (VH), and width (VW) measurements, were moderately to highly heritable in Yorkshire, with 0.46 ± 0.10, 0.55 ± 0.10, 0.31 ± 0.09, respectively, whereas these estimates were low to moderate in Landrace, with 0.16 ± 0.09, 0.24 ± 0.11, and 0.08 ± 0.06, respectively. Genetic correlations within VS traits were very high for both breeds, with the lowest of 0.67 ± 0.29 for VH and VW for Landrace. Genome-wide association studies (GWAS) for Landrace, reveled genomic region associated with VS traits on Sus scrofa chromosome (SSC) 2 (154-157 Mb), 7 (107-110 Mb), 8 (4-6 Mb), and 10 (8-19 Mb). For Yorkshire, genomic regions on SSC 1 (87-91 and 282-287 Mb) and 5 (67 Mb) were identified. All regions explained at least 3.4% of the genetic variance. Accuracies of genomic prediction were moderate in Landrace, ranging from 0.30 (VH) to 0.61 (VA), and lower for Yorkshire, with 0.07 (VW) to 0.11 (VH). Between-breed and multi-breed genomic prediction accuracies were low. Conclusions: Our findings suggest that VS traits are heritable in Landrace and Yorkshire gilts. Genomic analyses show that major QTL control these traits, and they differ between breed. Genomic information can be used to increase genetic gains for these traits in gilts. Additional research must be done to validate the GWAS and genomic prediction results reported in our study.

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Section: Genome-wide Association Analysissupporting

confidence: 69%

Genetic and genomic characterization of vulva size traits in Yorkshire and Landrace gilts

Corredor

Sanglard

Leach³

et al. 2020

BMC Genet

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“…It was recently implicated as the target of the tumor suppressor BAP1 that triggers apoptosis following exposure to genotoxic stress 40 . UNC5B is a netrin family receptor that mediates guidance of the vascular system as well as other cell types 41,42 . It encodes a repulsive netrin whose disruption results in aberrant extension, branching and navigation of affected cells 41 .…”

Section: Discussionmentioning

confidence: 99%

A catalog of cis-regulatory mutations in 12 major cancer types

Cheng

Vermeulen

Rollins-Green

et al. 2019

Preprint

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39Despite the recent availability of complete genome sequences of tumors from thousands of 40 patients, isolating disease-causing (driver) non-coding mutations from the plethora of somatic 41 variants is notoriously challenging, and only a handful of validated examples exist. By integrating 42 whole-genome sequencing, gene expression, chromatin accessibility, and genetic data from 43 TCGA, we identified 301 non-coding somatic mutations that affect gene expression in cis. These 44 mutations cluster into 36 hotspot regions with diverse molecular mechanisms of gene expression 45 regulation. We further show that these mutations have hallmark features of noncoding drivers; 46

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“…UNC5B is a member of the UNC5 receptor family that plays a major role in neuronal guidance via Netrin ligand binding (Seiradake et al 2016). However, UNC5B is especially involved in angiogenetic processes, being highly expressed in developing blood vessels (Lu et al 2004;Navankasattusas et al 2008;Tai-Nagara et al 2017). UNC5B acts as a repulsive receptor upon netrin-1 binding in vascular morphogenesis (Lu et al 2004) or FLRT2 binding in the placental labyrinth (Tai-Nagara et al 2017).…”

Section: Robo4mentioning

confidence: 99%

Structure and Function of Roundabout Receptors

Bisiak

McCarthy

2019

Subcellular Biochemistry

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The creation of complex neuronal networks relies on ligand-receptor interactions that mediate attraction or repulsion towards specific targets. Roundabouts comprise a family of single-pass transmembrane receptors facilitating this process upon interaction with the soluble extracellular ligand Slit protein family emanating from the midline. Due to the complexity and flexible nature of Robo receptors, their overall structure has remained elusive until now. Recent structural studies of the Robo1 and Robo2 ectodomains have provided the basis for a better understanding of their signalling mechanism. These structures reveal how Robo receptors adopt an auto-inhibited conformation on the cell surface that can be further stabilised by cis and/or trans oligmerisation arrays. Upon Slit-N binding Robo receptors must undergo a conformational change for Ig4 mediated dimerisation and signaling, probably via endocytosis. Furthermore, it's become clear that Robo receptors do not only act alone, but as large and more complex cell surface receptor assemblies to manifest directional and growth effects in a concerted fashion. These context dependent assemblies provide a mechanism to fine tune attractive and repulsive signals in a combinatorial manner required during neuronal development. While a mechanistic understanding of Slit mediated Robo signaling has advanced significantly further structural studies on larger assemblies are required for the design of new experiments to elucidate their role in cell surface receptor complexes. These will be necessary to understand the role of Slit-Robo signaling in neurogenesis, angiogenesis, organ development and cancer progression. In this chapter, we provide a review of the current knowledge in the field with a particular focus on the Roundabout receptor family.

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Placental labyrinth formation in mice requires endothelial FLRT2–UNC5B signaling

Cited by 26 publications

References 44 publications

Genetic and genomic characterization of vulva size traits in Yorkshire and Landrace gilts

Genetic and genomic characterization of vulva size traits in Yorkshire and Landrace gilts

A catalog of cis-regulatory mutations in 12 major cancer types

Structure and Function of Roundabout Receptors

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