Inverted formin 2 regulates intracellular trafficking, placentation, and pregnancy outcome.
Healthy pregnancy depends on proper placentation-including proliferation, differentiation, and invasion of trophoblast cells-which, if impaired, causes placental ischemia resulting in intrauterine growth restriction and preeclampsia. Mechanisms regulating trophoblast invasion, however, are unknown. We report that reduction of Inverted formin 2 (INF2) alters intracellular trafficking and significantly impairs invasion in a model of human extravillous trophoblasts. Furthermore, global loss of Inf2 in mice recapitulates maternal and fetal phenotypes of placental insufficiency. Inf2-/- dams have reduced spiral artery numbers and late gestational hypertension with resolution following delivery. Inf2-/- fetuses are growth restricted and demonstrate changes in umbilical artery Doppler consistent with poor placental perfusion and fetal distress. Loss of Inf2 increases fetal vascular density in the placenta and dysregulates trophoblast expression of angiogenic factors. Our data support a critical regulatory role for INF2 in trophoblast invasion-a necessary process for placentation-representing a possible future target for improving placentation and fetal outcomes.
Pubmed ID: 29309034 RIS Download
Research resources used in this publication
- BeWo (RRID:CVCL_0044) (cell line)
- Inf2tm1.1(KOMP)Vlcg/Inf2+ (RRID:MGI:5759294) (organism)
- SeaView (RRID:SCR_015059) (software resource)
- FigTree (RRID:SCR_008515) (data processing software)
- RAxML (RRID:SCR_006086) (software resource)
- MAFFT (RRID:SCR_011811) (software resource)
- HTR-8/SVneo (RRID:CVCL_7162) (cell line)
- C57BL/6J (RRID:IMSR_JAX:000664) (organism)
- SeaView (RRID:SCR_015059) (software resource)
- FigTree (RRID:SCR_008515) (data processing software)
- RAxML (RRID:SCR_006086) (software resource)
- MAFFT (RRID:SCR_011811) (software resource)
- Anti-INF2 (RRID:AB_11203139) (antibody)
- Lck antibody (RRID:AB_2249950) (antibody)
- Goat Anti-Mouse Proliferin Polyclonal antibody, Unconjugated (RRID:AB_2284428) (antibody)
- Goat Anti-Mouse Endomucin Affinity purified , Unconjugated (RRID:AB_2100035) (antibody)
- Anti-INF2 antibody produced in rabbit (RRID:AB_1078325) (antibody)
- MAL2 antibody (RRID:AB_1280985) (antibody)
- HTR-8/SVneo (RRID:CVCL_7162) (cell line)
- C57BL/6J (RRID:IMSR_JAX:000664) (organism)
Additional research tools detected in this publication
- ATCC (RRID:SCR_001672)
- Oxford Biomedical Research (RRID:SCR_006864)
- Imaris (RRID:SCR_007370)
- Thermo Fisher Scientific (RRID:SCR_008452)
- Ensembl (RRID:SCR_002344)
- Pfam (RRID:SCR_004726)
- BioVendor Laboratory Medicine (RRID:SCR_005143)
- PRISM (RRID:SCR_005375)
- PAML (RRID:SCR_014932)
- International Mouse Phenotyping Consortium (IMPC) (RRID:SCR_006158)
- C57BL/6NTac (RRID:MGI:2164831)
Antibodies used in this publication
- Anti-INF2 (RRID:AB_11203139)
- Lck antibody (RRID:AB_2249950)
- Goat Anti-Mouse Proliferin Polyclonal antibody, Unconjugated (RRID:AB_2284428)
- Goat Anti-Mouse Endomucin Affinity purified , Unconjugated (RRID:AB_2100035)
- Anti-INF2 antibody produced in rabbit (RRID:AB_1078325)
- MAL2 antibody (RRID:AB_1280985)
Associated grants
- Agency: NCRR NIH HHS, United States
Id: S10 RR029406
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This is a list of tools and resources that we have found mentioned in this publication.
ATCC (tool)
RRID:SCR_001672
Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsImaris (tool)
RRID:SCR_007370
Imaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentionsThermo Fisher Scientific (tool)
RRID:SCR_008452
Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsEnsembl (tool)
RRID:SCR_002344
Collection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.
View all literature mentionsPfam (tool)
RRID:SCR_004726
A database of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). Users can analyze protein sequences for Pfam matches, view Pfam family annotation and alignments, see groups of related families, look at the domain organization of a protein sequence, find the domains on a PDB structure, and query Pfam by keywords. There are two components to Pfam: Pfam-A and Pfam-B. Pfam-A entries are high quality, manually curated families that may automatically generate a supplement using the ADDA database. These automatically generated entries are called Pfam-B. Although of lower quality, Pfam-B families can be useful for identifying functionally conserved regions when no Pfam-A entries are found. Pfam also generates higher-level groupings of related families, known as clans (collections of Pfam-A entries which are related by similarity of sequence, structure or profile-HMM).
View all literature mentionsBioVendor Laboratory Medicine (tool)
RRID:SCR_005143
An Antibody supplier
View all literature mentionsPRISM (tool)
RRID:SCR_005375
THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsPAML (tool)
RRID:SCR_014932
Package of programs for phylogenetic analyses of DNA or protein sequences using maximum likelihood. PAML estimates parameters and tests hypotheses to study the evolutionary process from a phylogenetic tree.
View all literature mentionsInternational Mouse Phenotyping Consortium (IMPC) (tool)
RRID:SCR_006158
Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
View all literature mentionsC57BL/6NTac (tool)
RRID:MGI:2164831
laboratory mouse with name C57BL/6NTac from MGI.
View all literature mentionsGoat Anti-Mouse Proliferin Polyclonal antibody, Unconjugated (antibody)
RRID:AB_2284428
This polyclonal targets Mouse Proliferin
View all literature mentionsGoat Anti-Mouse Endomucin Affinity purified , Unconjugated (antibody)
RRID:AB_2100035
This unknown targets Mouse Endomucin
View all literature mentionsAnti-INF2 antibody produced in rabbit (antibody)
RRID:AB_1078325
This unknown targets Human C14orf151
View all literature mentionsBeWo (cell line)
RRID:CVCL_0044
Cell line BeWo is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsInf2tm1.1(KOMP)Vlcg/Inf2+ (organism)
RRID:MGI:5759294
Allele Detail: Targeted This is a legacy resource.
View all literature mentionsSeaView (software resource)
RRID:SCR_015059
Graphical user interface for multiple sequence alignment and molecular phylogeny. SeaView also generates phylogenetic trees.
View all literature mentionsFigTree (data processing software)
RRID:SCR_008515
A graphical viewer of phylogenetic trees and a program for producing publication-ready figures. It is designed to display summarized and annotated trees produced by BEAST.
View all literature mentionsRAxML (software resource)
RRID:SCR_006086
Software program for phylogenetic analyses of large datasets under maximum likelihood.
View all literature mentionsMAFFT (software resource)
RRID:SCR_011811
Software package as multiple alignment program for amino acid or nucleotide sequences. Can align up to 500 sequences or maximum file size of 1 MB. First version of MAFFT used algorithm based on progressive alignment, in which sequences were clustered with help of Fast Fourier Transform. Subsequent versions have added other algorithms and modes of operation, including options for faster alignment of large numbers of sequences, higher accuracy alignments, alignment of non-coding RNA sequences, and addition of new sequences to existing alignments.
View all literature mentionsHTR-8/SVneo (cell line)
RRID:CVCL_7162
Cell line HTR-8/SVneo is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsSeaView (software resource)
RRID:SCR_015059
Graphical user interface for multiple sequence alignment and molecular phylogeny. SeaView also generates phylogenetic trees.
View all literature mentionsFigTree (data processing software)
RRID:SCR_008515
A graphical viewer of phylogenetic trees and a program for producing publication-ready figures. It is designed to display summarized and annotated trees produced by BEAST.
View all literature mentionsRAxML (software resource)
RRID:SCR_006086
Software program for phylogenetic analyses of large datasets under maximum likelihood.
View all literature mentionsMAFFT (software resource)
RRID:SCR_011811
Software package as multiple alignment program for amino acid or nucleotide sequences. Can align up to 500 sequences or maximum file size of 1 MB. First version of MAFFT used algorithm based on progressive alignment, in which sequences were clustered with help of Fast Fourier Transform. Subsequent versions have added other algorithms and modes of operation, including options for faster alignment of large numbers of sequences, higher accuracy alignments, alignment of non-coding RNA sequences, and addition of new sequences to existing alignments.
View all literature mentionsGoat Anti-Mouse Proliferin Polyclonal antibody, Unconjugated (antibody)
RRID:AB_2284428
This polyclonal targets Mouse Proliferin
View all literature mentionsGoat Anti-Mouse Endomucin Affinity purified , Unconjugated (antibody)
RRID:AB_2100035
This unknown targets Mouse Endomucin
View all literature mentionsAnti-INF2 antibody produced in rabbit (antibody)
RRID:AB_1078325
This unknown targets Human C14orf151
View all literature mentionsHTR-8/SVneo (cell line)
RRID:CVCL_7162
Cell line HTR-8/SVneo is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentions
