Co-option of the Limb Patterning Program in Cephalopod Lens Development

AbstractAcross the Metazoa, similar genetic programs are found in the development of analogous, independently evolved, morphological features. The functional significance of this reuse and the underlying mechanisms of co-option remain unclear. Here we identify the co-option of the canonical bilaterian limb pattering program redeployed during cephalopod lens development, a functionally unrelated structure. We show radial expression of transcription factorsSP6-9/sp1, Dlx/dll, Pbx/exd, Meis/hth, and aPrdlhomolog in the squidDoryteuthis pealeii, similar to expression required inDrosophilalimb development. We assess the role of Wnt signaling in the cephalopod lens, a positive regulator in the developing limb, and find the regulatory relationship reversed, with ectopic Wnt signaling leading to lens loss. This regulatory divergence suggests that duplication of SP6-9 in cephalopods may mediate this co-option. These results suggest that the limb network does not exclusively pattern appendage outgrowth but is performing a more universal developmental function: radial patterning.

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Co-option of the limb patterning program in cephalopod eye development

BMC Biology ◽

10.1186/s12915-021-01182-2 ◽

2022 ◽

Vol 20 (1) ◽

Author(s):

Stephanie Neal ◽

Kyle J. McCulloch ◽

Francesca R. Napoli ◽

Christina M. Daly ◽

James H. Coleman ◽

...

Keyword(s):

Wnt Signaling ◽

Limb Development ◽

Lens Development ◽

Limb Patterning ◽

Regulatory Relationship ◽

Radial Patterning ◽

Refractive Lens ◽

Underlying Mechanisms ◽

Novel Structures

Abstract Background Across the Metazoa, similar genetic programs are found in the development of analogous, independently evolved, morphological features. The functional significance of this reuse and the underlying mechanisms of co-option remain unclear. Cephalopods have evolved a highly acute visual system with a cup-shaped retina and a novel refractive lens in the anterior, important for a number of sophisticated behaviors including predation, mating, and camouflage. Almost nothing is known about the molecular-genetics of lens development in the cephalopod. Results Here we identify the co-option of the canonical bilaterian limb patterning program during cephalopod lens development, a functionally unrelated structure. We show radial expression of transcription factors SP6-9/sp1, Dlx/dll, Pbx/exd, Meis/hth, and a Prdl homolog in the squid Doryteuthis pealeii, similar to expression required in Drosophila limb development. We assess the role of Wnt signaling in the cephalopod lens, a positive regulator in the developing Drosophila limb, and find the regulatory relationship reversed, with ectopic Wnt signaling leading to lens loss. Conclusion This regulatory divergence suggests that duplication of SP6-9 in cephalopods may mediate the co-option of the limb patterning program. Thus, our study suggests that this program could perform a more universal developmental function in radial patterning and highlights how canonical genetic programs are repurposed in novel structures.

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RSPO4-CRISPR alleviates liver injury and restores gut microbiota in a rat model of liver fibrosis

Communications Biology ◽

10.1038/s42003-021-01747-5 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Linghua Yu ◽

Linlin Wang ◽

Xiaojun Wu ◽

Huixing Yi

Keyword(s):

Liver Fibrosis ◽

Wnt Signaling ◽

Curative Effect ◽

Tissue Samples ◽

Fibrotic Liver ◽

Rrna Sequencing ◽

Liver Fibrogenesis ◽

Underlying Mechanisms ◽

16 S Rrna

AbstractWnt signaling dysfunction and gut dysbiosis may lead to liver fibrosis, yet the underlying mechanisms are not well elucidated. This study demonstrated the role of RSPO4, a Wnt signaling agonist, in liver fibrogenesis and its impact on the gut microbiome. RSPO4 gene in CCl4-induced fibrotic-liver rats was knockout by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system, with healthy rats served as the control. Tissue samples and hepatic stellate cells (HSCs) isolated from rats were examined for curative effect of RSPO4-CRISPR treatment. Fecal sample were collected and analyzed with 16 S rRNA sequencing. We found RSPO4-CRISPR relieved liver fibrosis in rats and reversed HSC activation. Further, results showed RSPO4-CRISPR tended to restore the microflora composition. Significance species between groups were identified. Bacteroides and Escherichia-Shigella were the key microbes in the model and negative group, whereas Lactobacillus, Romboutsia, and Lachnospiraceae NK4A136 group were abundant in the control. Notably, Bacteroidales S24-7 group and Ruminococcaceae UCG-005 were the significantly enriched in CRISPR group. We show that the microbiome of rats treated with RSPO4-CRISPR presents a trend towards the restoration of the original condition. Our findings pave a new way to evaluate the curative effect of liver fibrosis treatment.

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The Role of Wnt Signaling in Postnatal Tooth Root Development

Frontiers in Dental Medicine ◽

10.3389/fdmed.2021.769134 ◽

2021 ◽

Vol 2 ◽

Author(s):

Nicha Tokavanich ◽

Marc N. Wein ◽

Jeryl D. English ◽

Noriaki Ono ◽

Wanida Ono

Keyword(s):

Transcription Factors ◽

Wnt Signaling ◽

Signaling Pathway ◽

Root Development ◽

Root Formation ◽

Wnt Signaling Pathway ◽

Tooth Eruption ◽

Follicle Cells ◽

Tooth Root

Appropriate tooth root formation and tooth eruption are critical for achieving and maintaining good oral health and quality of life. Tooth eruption is the process through which teeth emerge from their intraosseous position to their functional position in the oral cavity. This temporospatial process occurs simultaneously with tooth root formation through a cascade of interactions between the epithelial and adjoining mesenchymal cells. Here, we will review the role of the Wnt system in postnatal tooth root development. This signaling pathway orchestrates the process of tooth root formation and tooth eruption in conjunction with several other major signaling pathways. The Wnt signaling pathway is comprised of the canonical, or Wnt/β-catenin, and the non-Canonical signaling pathway. The expression of multiple Wnt ligands and their downstream transcription factors including β-catenin is found in the cells in the epithelia and mesenchyme starting from the initiation stage of tooth development. The inhibition of canonical Wnt signaling in an early stage arrests odontogenesis. Wnt transcription factors continue to be present in dental follicle cells, the progenitor cells responsible for differentiation into cells constituting the tooth root and the periodontal tissue apparatus. This expression occurs concurrently with osteogenesis and cementogenesis. The conditional ablation of β-catenin in osteoblast and odontoblast causes the malformation of the root dentin and cementum. On the contrary, the overexpression of β-catenin led to shorter molar roots with thin and hypo-mineralized dentin, along with the failure of tooth eruption. Therefore, the proper expression of Wnt signaling during dental development is crucial for regulating the proliferation, differentiation, as well as epithelial-mesenchymal interaction essential for tooth root formation and tooth eruption.

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CircRNA_0079586 and circRNA_RanGAP1 are involved in the pathogenesis of intracranial aneurysms rupture by regulating the expression of MPO

Scientific Reports ◽

10.1038/s41598-021-99062-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhuang Zhang ◽

Rubo Sui ◽

Lili Ge ◽

Dongjian Xia

Keyword(s):

Endothelial Cells ◽

Signaling Pathways ◽

Intracranial Aneurysms ◽

Target Genes ◽

Regulatory Relationship ◽

Relative Expression Level ◽

Aneurysm Wall ◽

Microarray Screening ◽

Underlying Mechanisms

AbstractSeveral circRNAs have been reported to be dysregulated in human endothelial cells through sponging miRNAs. Previous reports demonstrated that MPO not only contributed to the formation and rupture of cerebral aneurysm but was also correlated with the degenerative remodeling predisposition to saccular intracranial aneurysm wall rupture, although its underlying mechanisms remain to be explored. Microarray screening was performed to compare the differential expression of circRNAs in the endothelial cells collected from UIAs and RIAs patients. Luciferase assays were used to explore the regulatory relationship between circRNAs and miRNAs, and between miRNAs and their target genes. Microarray screening analysis found a batch of up-regulated circRNAs in the endothelial cells harvested from RIAs patients, including circRNA-0079586 and circRNA-RanGAP1. Luciferase assays revealed the suppressive role of miR-183-5p/miR-877-3p in the expression of circRNA-0079586/circRNA-RanGAP1/MPO. And the expression of circRNA-0079586 and circRNA-RanGAP1 was respectively suppressed by the overexpression of miR-183-5p and miR-877-3p. And both the transfection of miR-183-5p and miR-877-3p mimics suppressed the relative expression level of MPO mRNA. The expression of circRNA-0079586, circRNA-RanGAP1 and MPO was significantly activated in the endothelial cells collected from RIAs patients when compared with UIAs patients, whereas the expression of miR-183-5p and miR-877-3p was remarkably suppressed in the endothelial cells collected from RIAs patients when compared with UIAs patients. We further altered the expression of circRNA-0079586 and circRNA-RanGAP1 using siRNA and overexpression in HUVECS, and the expression of circRNA-0079586 and circRNA-RanGAP1 was significantly and negatively correlated with the expression of miR-183-5p and miR-877-3p, but positively correlated with the expression of MPO under different conditions. In this study, we established two MPO-modulating signaling pathways of circRNA_0079586/miR-183-5p/MPO and circRNA_RanGAP1/miR-877-3p/MPO. These two signaling pathways are involved in the pathogenesis of intracranial aneurysms rupture.

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A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila

PLoS Genetics ◽

10.1371/journal.pgen.1009926 ◽

2021 ◽

Vol 17 (11) ◽

pp. e1009926

Author(s):

Flavia A. Graca ◽

Natalie Sheffield ◽

Melissa Puppa ◽

David Finkelstein ◽

Liam C. Hunt ◽

...

Keyword(s):

Transcription Factors ◽

Skeletal Muscles ◽

Large Scale ◽

Body Wall ◽

Glycolytic Enzymes ◽

Developmental Growth ◽

Transcriptional Changes ◽

Atrophy And Hypertrophy ◽

Underlying Mechanisms

Myofiber atrophy occurs with aging and in many diseases but the underlying mechanisms are incompletely understood. Here, we have used >1,100 muscle-targeted RNAi interventions to comprehensively assess the function of 447 transcription factors in the developmental growth of body wall skeletal muscles in Drosophila. This screen identifies new regulators of myofiber atrophy and hypertrophy, including the transcription factor Deaf1. Deaf1 RNAi increases myofiber size whereas Deaf1 overexpression induces atrophy. Consistent with its annotation as a Gsk3 phosphorylation substrate, Deaf1 and Gsk3 induce largely overlapping transcriptional changes that are opposed by Deaf1 RNAi. The top category of Deaf1-regulated genes consists of glycolytic enzymes, which are suppressed by Deaf1 and Gsk3 but are upregulated by Deaf1 RNAi. Similar to Deaf1 and Gsk3 overexpression, RNAi for glycolytic enzymes reduces myofiber growth. Altogether, this study defines the repertoire of transcription factors that regulate developmental myofiber growth and the role of Gsk3/Deaf1/glycolysis in this process.

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Canonical Wnt signaling Is Involved in Anterior Regeneration of the Annelid Aeolosoma viride

10.1101/2020.03.01.972448 ◽

2020 ◽

Author(s):

Cheng-Yi Chen ◽

Wei-Ting Yueh ◽

Jiun-Hong Chen

Keyword(s):

Wnt Signaling ◽

Wnt Pathway ◽

Wound Closure ◽

Tissue Level ◽

Canonical Wnt Signaling ◽

Blastemal Cell ◽

Underlying Mechanisms ◽

Canonical Wnt ◽

Anterior Regeneration

AbstractAnnelids are regenerative animals, but the underlying mechanisms await to be discovered. Because Wnt pathway is involved in animal regeneration to varying extents, we used Aeolosoma viride to interrogate whether and how this pathway plays a role in annelid anterior regeneration. We found that the expression of wnt4, β-catenin and nuclear-localized β-catenin protein were up-regulated during blastemal formation and down-regulated as anterior structures gradually reformed. Consistent with potential Wnt activities in the blastema, treatments with either Wnt pathway activator (azakenpaullone) or inhibitor (XAV939) inhibited head regeneration, which further supports a role of Wnt pathway during anterior regeneration. Detailed tissue-level examines demonstrated that wound closure and blastemal cell proliferation were impaired by over-activating the pathway, and that neuronal and musculature differentiation were affected under Wnt inhibition. Combined, gene expression and chemical inhibitor data suggest the presence of dynamic Wnt activities at different anterior regeneration stages: an initial low activity may be required for wound closure, and the following activation may signal blastemal formation and cell differentiation. In a nutshell, we propose that the canonical Wnt signaling regulates blastemal cellular responses during annelid regeneration.

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Role of Retinoic Acid Signaling, FGF Signaling and Meis Genes in Control of Limb Development

Biomolecules ◽

10.3390/biom11010080 ◽

2021 ◽

Vol 11 (1) ◽

pp. 80

Author(s):

Marie Berenguer ◽

Gregg Duester

Keyword(s):

Retinoic Acid ◽

Limb Development ◽

Limb Bud ◽

Limb Patterning ◽

Genetic Studies ◽

Fgf8 Signaling ◽

Bud Initiation ◽

Limb Initiation ◽

Somitic Mesoderm

The function of retinoic acid (RA) during limb development is still debated, as loss and gain of function studies led to opposite conclusions. With regard to limb initiation, genetic studies demonstrated that activation of FGF10 signaling is required for the emergence of limb buds from the trunk, with Tbx5 and RA signaling acting upstream in the forelimb field, whereas Tbx4 and Pitx1 act upstream in the hindlimb field. Early studies in chick embryos suggested that RA as well as Meis1 and Meis2 (Meis1/2) are required for subsequent proximodistal patterning of both forelimbs and hindlimbs, with RA diffusing from the trunk, functioning to activate Meis1/2 specifically in the proximal limb bud mesoderm. However, genetic loss of RA signaling does not result in loss of limb Meis1/2 expression and limb patterning is normal, although Meis1/2 expression is reduced in trunk somitic mesoderm. More recent studies demonstrated that global genetic loss of Meis1/2 results in a somite defect and failure of limb bud initiation. Other new studies reported that conditional genetic loss of Meis1/2 in the limb results in proximodistal patterning defects, and distal FGF8 signaling represses Meis1/2 to constrain its expression to the proximal limb. In this review, we hypothesize that RA and Meis1/2 both function in the trunk to initiate forelimb bud initiation, but that limb Meis1/2 expression is activated proximally by a factor other than RA and repressed distally by FGF8 to generate proximodistal patterning.

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Control of mouse limb initiation and antero-posterior patterning by Meis transcription factors

Nature Communications ◽

10.1038/s41467-021-23373-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Irene Delgado ◽

Giovanna Giovinazzo ◽

Susana Temiño ◽

Yves Gauthier ◽

Aurelio Balsalobre ◽

...

Keyword(s):

Transcription Factors ◽

Limb Development ◽

Critical Factor ◽

Interaction Networks ◽

Lateral Plate Mesoderm ◽

Lateral Plate ◽

Hox Proteins ◽

Mouse Limb ◽

Limb Initiation

AbstractMeis1 and Meis2 are homeodomain transcription factors that regulate organogenesis through cooperation with Hox proteins. Elimination of Meis genes after limb induction has shown their role in limb proximo-distal patterning; however, limb development in the complete absence of Meis function has not been studied. Here, we report that Meis1/2 inactivation in the lateral plate mesoderm of mouse embryos leads to limb agenesis. Meis and Tbx factors converge in this function, extensively co-binding with Tbx to genomic sites and co-regulating enhancers of Fgf10, a critical factor in limb initiation. Limbs with three deleted Meis alleles show proximal-specific skeletal hypoplasia and agenesis of posterior skeletal elements. This failure in posterior specification results from an early role of Meis factors in establishing the limb antero-posterior prepattern required for Shh activation. Our results demonstrate roles for Meis transcription factors in early limb development and identify their involvement in previously undescribed interaction networks that regulate organogenesis.

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Response Interference as a Mechanism Underlying Implicit Measures

European Journal of Psychological Assessment ◽

10.1027/1015-5759.24.4.218 ◽

2008 ◽

Vol 24 (4) ◽

pp. 218-225 ◽

Cited By ~ 28

Author(s):

Bertram Gawronski ◽

Roland Deutsch ◽

Etienne P. LeBel ◽

Kurt R. Peters

Keyword(s):

Task Performance ◽

Psychological Research ◽

Implicit Measures ◽

Mediation Model ◽

Response Interference ◽

Relevant Evidence ◽

Moderated Mediation Model ◽

Stimulus Features ◽

Underlying Mechanisms

Over the last decade, implicit measures of mental associations (e.g., Implicit Association Test, sequential priming) have become increasingly popular in many areas of psychological research. Even though successful applications provide preliminary support for the validity of these measures, their underlying mechanisms are still controversial. The present article addresses the role of a particular mechanism that is hypothesized to mediate the influence of activated associations on task performance in many implicit measures: response interference (RI). Based on a review of relevant evidence, we argue that RI effects in implicit measures depend on participants attention to association-relevant stimulus features, which in turn can influence the reliability and the construct validity of these measures. Drawing on a moderated-mediation model (MMM) of task performance in RI paradigms, we provide several suggestions on how to address these problems in research using implicit measures.

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The More You Say, the Less They Hear

Journal of Media Psychology Theories Methods and Applications ◽

10.1027/1864-1105/a000135 ◽

2015 ◽

Vol 27 (4) ◽

pp. 159-169 ◽

Cited By ~ 3

Author(s):

Elsbeth D. Asbeek Brusse ◽

Marieke L. Fransen ◽

Edith G. Smit

Keyword(s):

Hearing Protection ◽

Entertainment Education ◽

Mediating Role ◽

Attitude Measures ◽

Underlying Mechanisms

Abstract. This study examined the effects of disclosure messages in entertainment-education (E-E) on attitudes toward hearing protection and attitude toward the source. In addition, the (mediating) role of the underlying mechanisms (i.e., transportation, identification, and counterarguing) was studied. In an experiment (N = 336), three different disclosure messages were compared with a no-disclosure condition. The results show that more explicit disclosure messages negatively affect transportation and identification and stimulate the generation of counterarguments. In addition, the more explicit disclosure messages affect both attitude measures via two of these processes (i.e., transportation and counterarguing). Less explicit disclosure messages do not have this effect. Implications of the findings are discussed.

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