Specific structure and unique function define the hemicentin

Xu, Xuehong; Xu, Meng; Zhou, Xin; Jones, Odell B.; Moharomd, Edward; Pan, Ya-min; Yan, Guifang; Anthony, Donald D.; Isaacs, Williams B.

doi:10.1186/2045-3701-3-27

Cited by 37 publications

(32 citation statements)

References 18 publications

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“…Three of the 5 genes upregulated by Gly alone ( i.e. , miR-495 , Hmcn1 and Tnfsf13b ) are involved in neurogenesis, tissue development and immune response functions, respectively (Farina et al 2007; Wu et al 2010; Xu et al 2013) (Table 2). Interestingly, Ppia , which is downregulated in Gly groups (Tables 2, 3), is involved in apoptosis and promotes neurodegeneration by initiating a pro-inflammatory pathway leading to neuronal damage and loss of synaptic connections (Nigro et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Soy glyceollins regulate transcript abundance in the female mouse brain

Bamji

Page

Patel

et al. 2015

Funct Integr Genomics

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Glyceollins (Gly), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Gly exhibits mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Gly on gene expression in the brain are unknown. For this study, we implanted 17-β estradiol (E2) or placebo slow-release pellets into ovariectomized CFW mice followed by 11 days of exposure to Gly or vehicle i.p. injections. We then performed a microarray on total RNA extracted from whole brain hemispheres and identified differentially expressed genes (DEGs) by a 2 × 2 factorial ANOVA with an FDR = 0.20. In total, we identified 33 DEGs with a significant E2 main effect, 5 DEGs with a significant Gly main effect, 74 DEGs with significant Gly and E2 main effects (but no significant interaction term), and 167 DEGs with significant interaction terms. Clustering across all DEGs revealed that transcript abundances were similar between the E2+Gly and E2-only treatments. However, gene expression after Gly-only treatment was distinct from both of these treatments and was generally characterized by higher transcript abundance. Collectively, our results suggest that whether Gly acts in the brain through ER-dependent or ER-independent mechanisms depends on the target gene.

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Section: Discussionmentioning

confidence: 99%

Soy glyceollins regulate transcript abundance in the female mouse brain

Bamji

Page

Patel

et al. 2015

Funct Integr Genomics

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“…The C. intestinalis gene annotated as HMCN1 is not a hemicentin, despite what the name implies. Hemicentins are very large molecules that typically have >40 consecutive Ig domains (Xu et al, 2013). Because of this, hemicentins may show regions of strong sequence similarity to distantly related Ig-superfamily members in BLAST searches, the basis of the initial homology assignment.…”

Section: Resultsmentioning

confidence: 99%

ACAM, a novel member of the neural IgCAM family, mediates anterior neural tube closure in a primitive chordate

Diaz

Mejares

Newman-Smith

et al. 2016

Developmental Biology

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The neural IgCAM family of cell adhesion molecules, which includes NCAM and related molecules, has evolved via gene duplication and alternative splicing to allow for a wide range of isoforms with distinct functions and homophilic binding properties. A search for neural IgCAMs in ascidians (Ciona intestinalis, Ciona savignyi, and Phallusia mammillata) has identified a novel set of truncated family members that, unlike the known members, lack fibronectin III domains and consist of only repeated Ig domains. Within the tunicates this form appears to be unique to the ascidians, and it was designated ACAM, for Ascidian Cell Adhesion Molecule. In C. intestinalis ACAM is expressed in the developing neural plate and neural tube, with strongest expression in the anterior sensory vesicle precursor. Unlike the two other conventional neural IgCAMs in C. intestinalis, which are expressed maternally and throughout the morula and blastula stages, ACAM expression initiates at the gastrula stage. Moreover, C. intestinalis ACAM is a target of the homeodomain transcription factor OTX, which plays an essential role in the development of the anterior central nervous system. Morpholino (MO) knockdown shows that ACAM is required for neural tube closure. In MO-injected embryos neural tube closure was normal caudally, but the anterior neuropore remained open. A similar phenotype was seen with overexpression of a secreted version of ACAM. The presence of ACAM in ascidians highlights the diversity of this gene family in morphogenesis and neurodevelopment.

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“…Mouse Hemicentin-1 is also a predicted target of POFUT2 (Du et al, 2010). Since hemicentins are important for maintaining the architectural integrity of vertebrate tissues and organs (reviewed in Xu et al (2013)), disruption of cell-ECM connections could also contribute to disorganization of epithelia in the Pofut2 mutants. However, since the mouse Hemicentin-1 knockout disrupts early cleavage divisions and results in pre-implantation lethality, loss of Pofut2 must not completely block Hemicentin-1 function (Xu and Vogel, 2011).…”

Section: Discussionmentioning

confidence: 99%

Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion

Benz

Nandadasa

Takeuchi

et al. 2016

Developmental Biology

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Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. The similarity between Pofut2 and Adamts9 mutants suggested that disruption of ADAMTS9 function could be responsible for the gastrulation defects observed in Pofut2 mutants. Consistent with this prediction, CRISPR/Cas9 knockout of POFUT2 in HEK293T cells blocked secretion of ADAMTS9. We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of the visceral endoderm and altered characteristics of the extraembryonic ectoderm. Consequently, loss of input from the extraembryonic ectoderm and/or compression of the epiblast by Reichert’s membrane blocks gastrulation. In the future, the Pofut2 and Adamts9 knockouts will be valuable tools for understanding how local changes in the properties of the extracellular matrix influence the organization of tissues during mammalian development.

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Specific structure and unique function define the hemicentin

Cited by 37 publications

References 18 publications

Soy glyceollins regulate transcript abundance in the female mouse brain

Soy glyceollins regulate transcript abundance in the female mouse brain

ACAM, a novel member of the neural IgCAM family, mediates anterior neural tube closure in a primitive chordate

Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion

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