Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins

Kiyozumi, Daiji; Takeichi, M; Nakano, Itsuko; Sato, Yuya; Fukuda, Tomohiko; Sekiguchi, Kiyotoshi

doi:10.1083/jcb.201203065

Cited by 52 publications

(76 citation statements)

References 34 publications

(98 reference statements)

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“…In pharyngeal arches, we find itga8 mRNA expression in mesenchyme adjacent to epithelial fras1 expression, suggesting that Itga8 and the FPC may interact at epithelial-mesenchymal boundaries in the face. Itga8 may interact with the FPC through several mechanisms, such as protein-protein adhesion, the proteins regulating one another, and/or co-regulating downstream targets; some of these mechanisms have been confirmed previously in mouse kidneys (Kiyozumi et al, 2012; Pitera et al, 2008). However, a survey of several candidate genes expressed during zebrafish facial development revealed no evidence for signal transduction downstream of fras1 or itga8 ; instead, adhesive interactions between the two proteins may be of particular importance.…”

Section: Introductionsupporting

confidence: 52%

“…Based on these data, we hypothesized that Fras1 and Itga8 shape facial morphology via a combination of tissue adhesive and/or regulatory interactions dependent upon the FPC, as has been indicated previously in mouse kidney (Kiyozumi et al, 2012; Pitera et al, 2008). To test this hypothesis, we first examined whether fras1 and/or itga8 regulate one another at the level of transcript expression.…”

Section: Resultsmentioning

confidence: 59%

“…In cell culture, Itga8 binds directly to the Arg-Gly-Asp (RGD)-containing domain of Frem1, and RGD-binding is necessary for Frem1-mediated cell adhesion (Kiyozumi et al, 2005). However the Frem1 RGD domain is dispensable for mouse kidney, skin, and limb development (Kiyozumi et al, 2012). In mouse kidneys, Itga8 also binds directly to the RGD domain of Nephronectin (Npnt), another ECM glycoprotein (Brandenberger, 2001; Sato et al, 2009); Npnt binds to Frem1 (Kiyozumi et al, 2012), and Npnt is itself required for kidney formation (Linton et al, 2007), suggesting that Npnt may help to link Itga8 with the FPC.…”

Section: Introductionmentioning

confidence: 99%

“…However the Frem1 RGD domain is dispensable for mouse kidney, skin, and limb development (Kiyozumi et al, 2012). In mouse kidneys, Itga8 also binds directly to the RGD domain of Nephronectin (Npnt), another ECM glycoprotein (Brandenberger, 2001; Sato et al, 2009); Npnt binds to Frem1 (Kiyozumi et al, 2012), and Npnt is itself required for kidney formation (Linton et al, 2007), suggesting that Npnt may help to link Itga8 with the FPC. However, it was unclear from previous work how important Itga8 is to FPC-mediated epithelial mesenchymal interactions, and which tissues require Itga8-FPC interaction.…”

Section: Introductionmentioning

confidence: 99%

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Pharyngeal morphogenesis requires fras1 - itga8 -dependent epithelial-mesenchymal interaction

Talbot

Nichols

Yan

et al. 2016

Developmental Biology

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Both Fras1 and Itga8 connect mesenchymal cells to epithelia by way of an extracellular ‘Fraser protein complex’ that functions in signaling and adhesion; these proteins are vital to the development of several vertebrate organs. We previously found that zebrafish fras1 mutants have craniofacial defects, specifically, shortened symplectic cartilages and cartilage fusions that spare joint elements. During a forward mutagenesis screen, we identified a new zebrafish mutation, b1161, that we show here disrupts itga8, as confirmed using CRISPR-generated itga8 alleles. fras1 and itga8 single mutants and double mutants have similar craniofacial phenotypes, a result expected if loss of either gene disrupts function of the Fraser protein complex. Unlike fras1 mutants or other Fraser-related mutants, itga8 mutants do not show blistered tail fins. Thus, the function of the Fraser complex differs in the craniofacial skeleton and the tail fin. Focusing on the face, we find that itga8 mutants consistently show defective outpocketing of a late-forming portion of the first pharyngeal pouch, and variably express skeletal defects, matching previously characterized fras1 mutant phenotypes. In itga8 and fras1 mutants, skeletal severity varies markedly between sides, indicating that both mutants have increased developmental instability. Whereas fras1 is expressed in epithelia, we show that itga8 is expressed complementarily in facial mesenchyme. Paired with the observed phenotypic similarity, this expression indicates that the genes function in epithelial-mesenchymal interactions. Similar interactions between Fras1 and Itga8 have previously been found in mouse kidney, where these genes both regulate Nephronectin (Npnt) protein abundance. We find that zebrafish facial tissues express both npnt and the Fraser gene fibrillin2b (fbn2b), but their transcript levels do not depend on fras1 or itga8 function. Using a revertible fras1 allele, we find that the critical window for fras1 function in the craniofacial skeleton is between 1.5 and 3 days post fertilization, which coincides with the onset of fras1-dependent and itga8-dependent morphogenesis. We propose a model wherein Fras1 and Itga8 interact during late pharyngeal pouch morphogenesis to sculpt pharyngeal arches through epithelial-mesenchymal interactions, thereby stabilizing the developing craniofacial skeleton.

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Section: Introductionsupporting

confidence: 52%

Section: Resultsmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharyngeal morphogenesis requires fras1 - itga8 -dependent epithelial-mesenchymal interaction

Talbot

Nichols

Yan

et al. 2016

Developmental Biology

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“…Frem2 and related proteins have been implicated in epithelium-mesenchyme adhesion and mutations in these genes underlie Fraser's syndrome (Smyth and Scambler, 2005). Frem proteins are required for the proper incorporation of nephronectin, an integrin ligand required for kidney morphogenesis, into the ECM (Kiyozumi et al, 2012). The sea urchin ortholog of nephronectin (npnt) is expressed selectively by PMCs during gastrulation and might play an important role in PMC-substrate interactions.…”

Section: Adhesion/migration Proteins Nephronectinmentioning

confidence: 99%

Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins

Azhari¹,

Shashikant²,

McManus³

et al. 2014

Development

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There was an error published in Development 141, 950-961.Column M of supplementary Table S1 contained an error and has been replaced. The authors apologise to readers for this mistake. ABSTRACT A central challenge of developmental and evolutionary biology is to understand the transformation of genetic information into morphology. Elucidating the connections between genes and anatomy will require model morphogenetic processes that are amenable to detailed analysis of cell/tissue behaviors and to systems-level approaches to gene regulation. The formation of the calcified endoskeleton of the sea urchin embryo is a valuable experimental system for developing such an integrated view of the genomic regulatory control of morphogenesis. A transcriptional gene regulatory network (GRN) that underlies the specification of skeletogenic cells (primary mesenchyme cells, or PMCs) has recently been elucidated. In this study, we carried out a genome-wide analysis of mRNAs encoded by effector genes in the network and uncovered transcriptional inputs into many of these genes. We used RNA-seq to identify >400 transcripts differentially expressed by PMCs during gastrulation, when these cells undergo a striking sequence of behaviors that drives skeletal morphogenesis. Our analysis expanded by almost an order of magnitude the number of known (and candidate) downstream effectors that directly mediate skeletal morphogenesis. We carried out genome-wide analysis of (1) functional targets of Ets1 and Alx1, two pivotal, early transcription factors in the PMC GRN, and (2) functional targets of MAPK signaling, a pathway that plays an essential role in PMC specification. These studies identified transcriptional inputs into >200 PMC effector genes. Our work establishes a framework for understanding the genomic regulatory control of a major morphogenetic process and has important implications for reconstructing the evolution of biomineralization in metazoans. 2542

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In Situ Detection of Integrin Ligands

2014

Self Cite

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Integrins are cell surface receptors for cell adhesion. Integrin‐mediated cell adhesion regulates various cellular processes, including cell survival, migration, proliferation, and differentiation. In vivo, ligands for integrins are immobilized within extracellular matrices, insoluble sheet‐like or fibrous supramolecular complexes that associate with or surround cells. To better understand the molecular basis of integrin‐mediated regulation of cellular behavior in vivo, it is of critical importance to collect information regarding the activities as well as spatial distributions of integrin ligands in situ. This unit describes a protocol for detecting the spatial distribution of the complement of integrin ligands in situ by overlaying soluble recombinant integrins. © 2014 by John Wiley & Sons, Inc.

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Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins

Abstract: QBRICK facilitates the integrin α8β1–dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin.

Cited by 52 publications

References 34 publications

Pharyngeal morphogenesis requires fras1 - itga8 -dependent epithelial-mesenchymal interaction

Pharyngeal morphogenesis requires fras1 - itga8 -dependent epithelial-mesenchymal interaction

Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins

In Situ Detection of Integrin Ligands

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