Fraser Complex Research Articles

The Fraser Complex Proteins (Frem1, Frem2, and Fras1) Can Form Anchoring Cords in the Absence of AMACO at the Dermal–Epidermal Junction of Mouse Skin

AMACO (VWA2 protein), secreted by epithelial cells, is strongly expressed at basement membranes when budding or invagination occurs in embryos. In skin, AMACO associates with proteins of the Fraser complex, which form anchoring cords. These, during development, temporally stabilize the dermal-epidermal junction, pending the formation of collagen VII-containing anchoring fibrils. Fraser syndrome in humans results if any of the core members of the Fraser complex (Fras1, Frem1, Frem2) are mutated. Fraser syndrome is characterized by subepidermal blistering, cryptophthalmos, and syndactyly. In an attempt to determine AMACO function, we generated and characterized AMACO-deficient mice. In contrast to Fraser complex mutant mice, AMACO-deficient animals lack an obvious phenotype. The mutually interdependent basement membrane deposition of the Fraser complex proteins, and the formation of anchoring cords, are not affected. Furthermore, hair follicle development in newborn AMACO-deficient mice showed no gross aberration. Surprisingly, it appears that, while AMACO is a component of the anchoring cords, it is not essential for their formation or function.

Anchoring Cords: A Distinct Suprastructure in the Developing Skin

AMACO (VWA2 protein) is a basement membrane-associated protein secreted by epithelial cells. It is strongly expressed when invagination or budding occurs during development. AMACO associates with the Fraser complex, which when mutated causes Fraser syndrome, characterized by subepidermal blistering, cryptophthalmos, and syndactyly. The core Fraser complex proteins FRAS1, FREM1, and FREM2 localize at the dermal‒epidermal junction and mediate adhesion to the underlying dermis during embryonic development. Earlier transmission electron microscopy studies of adult mouse skin showed clustered AMACO deposition below the lamina densa. In this study, we report a distinct cord-like suprastructure in the neonate dermis to which AMACO- and Fraser complex‒associated proteins contribute. We propose anchoring cords to designate the suprastructure. Anchoring cords have a diameter of 60 nm when immunolabeled, originate from the basement membrane, and extend several microns into the dermis. In normal skin, they are evident after immunogold electron microscopy and are strikingly appreciated in thicker sections. In recessive dystrophic epidermolysis bullosa skin, they are directly visible where collagen VII anchoring fibrils are ablated. Immunofluorescence and coimmunoprecipitation of skin extracts identify a direct interaction of FREM2 and AMACO.

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

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.

AMACO Is a Component of the Basement Membrane–Associated Fraser Complex

Fraser syndrome (FS) is a phenotypically variable, autosomal recessive disorder characterized by cryptophthalmus, cutaneous syndactyly, and other malformations resulting from mutations in FRAS1, FREM2, and GRIP1. Transient embryonic epidermal blistering causes the characteristic defects of the disorder. Fras1, Frem1, and Frem2 form the extracellular Fraser complex, which is believed to stabilize the basement membrane. However, several cases of FS could not be attributed to mutations in FRAS1, FREM2, or GRIP1, and FS displays high clinical variability, suggesting that there is an additional genetic, possibly modifying contribution to this disorder. An extracellular matrix protein containing VWA-like domains related to those in matrilins and collagens (AMACO), encoded by the VWA2 gene, has a very similar tissue distribution to the Fraser complex proteins in both mouse and zebrafish. Here, we show that AMACO deposition is lost in Fras1-deficient zebrafish and mice and that Fras1 and AMACO interact directly via their chondroitin sulfate proteoglycan (CSPG) and P2 domains. Knockdown of vwa2, which alone causes no phenotype, enhances the phenotype of hypomorphic Fras1 mutant zebrafish. Together, our data suggest that AMACO represents a member of the Fraser complex.

A New Component of the Fraser Complex

SummaryIn embryos, the Fraser Complex (FC) mediates epithelial-connective tissue interactions. Loss of expression of FC components leads to Fraser Syndrome (FS) in which cohesion of epithelial tissues and stroma is perturbed. Using zebrafish, Richardson et al (in this issue) identified the protein AMACO in the FC. We discuss the utility of zebrafish in determining FC functions and identifying FS targets.

Evolution of a crustal‐scale transpressive shear zone in the Albany–Fraser Orogen, SW Australia: 2. Tectonic history of the Coramup Gneiss and a kinematic framework for Mesoproterozoic collision of the West Australian and Mawson cratons

AbstractWithin the Albany–Fraser Orogen of southwestern Australia, the Coramup Gneiss is a NE–SW trending zone of high‐strain rocks that preserves a detailed record of orogenesis related to Mesoproterozoic convergence of the West Australian and Mawson cratons. New structural, metamorphic and U–Pb SHRIMP zircon age data establish that the Coramup Gneiss underwent high‐grade tectonism during both Stage I (c. 1290 Ma) and Stage II (c. 1170 Ma) of the Albany–Fraser Orogeny. Stage I commenced with c. 1300 Ma high‐T, low‐P M1a metamorphism during extension, and the formation of small‐scale ptygmatic folds within a subhorizontal S1a gneissosity. High‐P M1b metamorphism at c. 1290 Ma was accompanied by the transposition and shearing of S1a into a composite, shallow SE‐dipping S1b foliation, and the development of tight recumbent F1b folds with S1‐parallel axial surfaces and asymmetries indicating NW‐directed thrusting. The preservation of a similar P–T–time record in the Fraser Complex (NE of the Coramup Gneiss) is consistent with large‐scale, NW‐directed Stage I thrusting of the Mawson Craton margin over the south‐eastern edge of the West Australian Craton. Stage II tectonism in the western Coramup Gneiss involved high‐T, low‐P M2a metamorphism and the formation of subvertical SE‐dipping D2 shear zones, shallow SW‐plunging L2 mineral stretching lineations, and NW‐verging F2 folds with S2‐parallel axial surfaces. A synkinematic pegmatite dyke emplaced into a D2 shear zone yielded a U–Pb SHRIMP zircon age of 1168 ± 12 Ma. Kinematic indicators suggest a combination of pure shear flattening perpendicular to S2, and dextral simple shear. However, contemporaneous structures elsewhere in the Albany–Fraser Orogen are consistent with continued NW–SE convergence at craton‐scale during Stage II, and oblique compression in the Coramup Gneiss is attributed to the arcuate geometry of the orogen‐scale deformation front.

Mesoproterozoic Fraser Complex: Geochemical evidence for multiple subduction‐related sources of lower crustal rocks in the Albany‐Fraser Orogen, Western Australia

The 1300 Ma Fraser Complex in the Albany‐Fraser Orogen of Western Australia is a thrust stack of mainly gabbroic rocks metamorphosed to granulite facies. This package of fault‐bounded units was elevated from a deep crustal level onto the margin of the Yilgarn Craton during continental collision between the Mawson and Yilgarn Cratons. Incompatible trace‐element distributions demand at least three mantle sources. Primitive‐mantle‐normalised incompatible‐element distributions show strong negative Ta–Nb anomalies, typical of subduction‐derived magmas. Three lines of evidence indicate that the mafic magmas did not acquire these anomalies by assimilation of crustal rocks: (i) major‐element compositions do not allow appreciable contamination with felsic material; (ii) Ni contents of many mafic rocks are too high for a significant contribution from a felsic assimilant; and (iii) Sr and Nd isotopic data support a largely juvenile source for the magmas that produced the Fraser Complex. Hence, the Ta–Nb anomalies are interpreted to reflect subduction‐related magmatic sources. On multielement diagrams, depletions in Sr, Eu, P, and Ti can be explained by fractional crystallisation, whereas Th and Rb depletions in many of the Fraser Complex rocks probably reflect losses during granulite‐facies metamorphism. These results suggest that the lower crust in this region at 1300 Ma was dominantly of arc origin, and there is no evidence to support mantle plume components. The Fraser Complex is interpreted as remnants of oceanic arcs that were swept together and tectonically interleaved with the margin of the Mawson Craton just before, or during, collision with the Yilgarn Craton at 1300 Ma.

Relationships between magmatism, metamorphism and deformation in the Fraser Complex, Western Australia: Constraints from new SHRIMP U–Pb zircon geochronology

SHRIMP U–Pb zircon isotopic data have been obtained for four samples collected from granitoids and paragneisses in the Fraser Complex, a large composite metagabbroic body cropping out in the Mesoproterozoic Albany‐Fraser Orogen of Western Australia. The data are combined with the results of field mapping and petrographic analysis to revise a model for the geological evolution of the Fraser Complex. Three main phases of deformation are recognised in the Fraser Complex (D1–3) associated with two metamorphic events (M1–2), which involve four distinguishable episodes of recrystallisation. The first metamorphic event recognised (M1a/D1) reached granulite facies and is characterised by peak T ≥800°C and P = 600–700 MPa. A syn‐M1a/D1 charnockite has a U–Pb SHRIMP zircon age of 1301 ± 6 Ma, which also provides an estimate for the age of intrusion of Fraser Complex gabbroic rocks. Disequilibrium textures comprising randomly oriented minerals (M1b), consistent with approximately isobaric cooling, formed in various lithologies in the interval between D1 and D2. Post‐D1, pre‐D2 granites intruded at 1293 ± 8 Ma and were foliated during the D2 event, which culminated in the burial of the Fraser Complex to depths equivalent to 800–1000 MPa. Following burial, pyroxene granulites on the western boundary of the complex were pervasively retrogressed to garnet amphibolite (M2a). An igneous crystallisation age of 1288 ± 12 Ma from a syn‐M2a aplite dyke suggests that retrogression may have occurred only a few millions of years after the peak of granulite facies metamorphism. Exhumation to depths of less than ∼400 MPa occurred within ∼20–30 million years of the M2a pressure peak. Associated deformation (D3) is characterised by the development of mylonite and transitional greenschist/amphibolite facies disequilibrium textures (M2b).

Field characteristics, petrography, and geochronology of the Hohonu Batholith and the adjacent Granite Hill Complex, North Westland, New Zealand

Detailed geological mapping, petrography, geochemistry, and geochronological studies in the Hohonu Batholith, North Westland, have identified 10 granitoid plutons emplaced during three intrusive episodes. The earliest episode is represented by a single dated Paleozoic pluton, Summit Granite (new) (381.2 ± 7.3 Ma), which is correlated with a discrete pulse of Mid—Late Devonian plutonism recognised in the Karamea Batholith. The undated Mount Graham Granite (new) is also likely to be Paleozoic, based on chemical and petrographic characteristics. The bulk of the batholith (seven plutons) was emplaced in the mid Cretaceous (114–109 Ma) and comprises two related, yet distinct, geochemical suites, which correlate with the previously defined Rahu Suite. The plutons identified are (from north to south): Pah Point Granite; Jays Creek Granodiorite (new); Uncle Bay Tonalite; Te Kinga Monzogranite; Deutgam Granodiorite; Turiwhate Granodiorite (new); and Arahura Granite (new). Mid‐Cretaceous plutonism in the Western Province is considered to be the result of crustal thinning and extension following overthickening during collision of the Early Cretaceous Median Tectonic Zone volcanic arc. Late Cretaceous alkaline activity is represented by the emplacement of the A‐type French Creek Granite at 81.7 ± 1.8 Ma, contemporaneous with intrusion of a major swarm of doleritic‐lamprophyric dikes—the Hohonu Dike Swarm. These events correlate with the first appearance of oceanic crust in the Tasman Sea. The Granite Hill Complex is a suite of amphibolite facies gneisses occurring as an uplifted wedge between the Alpine Fault and the Hohonu Batholith. These gneisses are considered to represent an extension of the Fraser Complex to the south. A detailed understanding of their geological affinities and history is yet to be established.

Chronology and evolution of the Middle Proterozoic Albany‐Fraser Orogen, Western Australia

Geochemical and Sm‐Nd isotopic data, and 19 ion‐microprobe U‐Pb zircon dates are reported for gneiss and granite from the eastern part of the Albany‐Fraser Orogen. The orogen is dominated by granitic rocks derived from sources containing both Late Archaean and mantle‐derived components. Four major plutonic episodes have been identified at ca 2630 Ma, 1700–1600 Ma, ca 1300 Ma and ca 1160 Ma. Orthogneiss, largely derived from ca 2630 Ma and 1700–1600 Ma granitic precursors, forms a belt along the southeastern margin of the Yilgarn Craton. These rocks, together with gabbro of the Fraser Complex, were intruded by granitic magmas and metamorphosed in the granulite facies at ca 1300 Ma. They were then rapidly uplifted and transported westward along low‐angle thrust faults over the southeastern margin of the Yilgarn Craton. Between ca 1190 and 1130 Ma, granitic magmas were intruded throughout the eastern part of the orogen. These new data are integrated into a review of the geological evolution of the Albany‐Fraser Orogen and adjacent margin of eastern Antarctica, and possibly related rocks in the Musgrave Complex and Gawler Craton.

Late Jurassic‐Early Cretaceous metamorphic age of Fraser Complex migmatite, Westland, New Zealand

Abstract Discordant U‐Pb zircon data from a migmatitic leucosome in amphibolite facies gneiss of the Fraser Complex define a 157 ± 21 Ma concordia lower intercept date interpreted as the age of peak metamorphism. An upper intercept date of 735 ± 100 Ma indicates inheritance of Proterozoic zircon. The mid‐Mesozoic age for high‐grade metamorphism does not support the existence of a regional Precambrian gneiss basement, incorporating the Fraser Complex and other gneissic rocks in Westland, as suggested by earlier workers. Early Paleozoic Greenland Group, of subgreenschist facies regional metamorphic grade, is separated from Fraser Complex by the Fraser Fault. This structural relationship is similar to that described from Cretaceous metamorphic core complexes in the New Zealand Western Province where lower plate amphibolite facies metamorphic rocks are separated from upper plate Greenland Group strata by detachment faults. Although the mid‐Mesozoic age of metamorphism reported here suggests an affinity with t...

Isotopic evidence on the age and origin of the Fraser Complex, Western Australia: a sample of Mid-Proterozoic lower crust

SmNd, RbSr and Pb isotopic data have been obtained for a variety of samples from within and around the Fraser Complex, a large (> 400 × 30 km) composite body of metagabbro which is a major component of the Proterozoic Albany-Fraser Orogen. Granites to the north and east of the complex and a granite sheet near its centre have SmNd model ages ( t DM) of ∼2000 to ∼ 2300 Ma, similar to values recorded in the western portion of the orogen. SmNd data for Fraser Complex gabbros scatter significantly on an isochron plot, but well-preserved igneous minerals extracted from one sample give 1291 ± 21 Ma with initial ϵ Nd = -1.3 ± 0.2. RbSr for the biotite-rock pair gives a cooling age of 1268 ± 20 Ma with initial 87Sr/ 86Sr≈0.706. Slices cut from a mixed gneiss/ amphibolite zone of ductile deformation and retrogression along the western margin of the complex give a ∼ 1300-Ma Pb/Pb date for final tectonic emplacement. Intrusion, granulite-facies metamorphism and upper-crustal tectonic emplacement of the complex were probably all achieved within ≤ 30 Ma. SmNd and RbSr characteristics of the western deformation zone suggest flushing by large volumes of fluid derived from a moderately depleted mantle source (ϵ Nd ≈ + 2.4; ϵ Sr, ≈ − 5 at 1300 Ma). The precursors to the Fraser Complex could have been derived from the same (or a similar) source at ∼ 1900 Ma.

The Fraser Complex: High‐grade metamorphic, igneous and mylonitic rocks in central Westland, New Zealand

Abstract Diverse, mappable, and variably mylonitised high‐grade gneisses and granitoids, and lamprophyre, trachyte, and basalt dikes comprise the Fraser Complex, which is a new name proposed to replace the existing Fraser Formation. Sillimanite‐bearing pelitic gneisses have an upper amphibolite facies metapelitic mineralogy, indicating temperatures >600°C. Quartzofeldspathic gneisses, lacking sillimanite, are migmatitic, and hornblende gneisses have a diverse epidote‐amphibolite mineralogy. The high‐grade gneisses form a metamorphic suite within the Fraser Complex. Granite, granodiorite, and tonalite are intrusive into the high‐grade gneiss suite, and may have been derived from partial melts of the high‐grade gneisses. Swarms of camptonite lamprophyre, trachyte, and basalt dikes intrude the high‐grade gneisses and the granitoids. Mylonite zones now envelop the gneisses, granitoids, and dikes, and mylonitic deformation occurred at mid‐greenschist facies conditions and resulted in some retrogressive alterat...