Biology subjects

Pedersen, L. B.

Publications and source records attributed to Pedersen, L. B..

18 recordsLinked to original sources

bioRxiv2026

Ancient environmental DNA reveals the distinct fingerprints of whaling and climate change on Antarctic marine biodiversity

The Southern Ocean is a disproportionately large contributor to Earth system processes, playing a crucial role in the global transport of carbon, oxygen and heat. It also hosts enormous seasonal biological productivity that supports diverse endemic marine biodiversity. Industrial whaling in the first half of the 20th century and recent human-driven climate change have both profoundly altered Antarctic ecosystems, but ecological surveys of these impacts are limited to well-known taxa in the short period since monitoring began. Here, we analysed five sediment records to reconstruct more than two centuries of ecosystem change across the Western Antarctic Peninsula, spanning periods before and during major human impacts. Environmental DNA metabarcoding of these records revealed substantial biodiversity shifts, with change accelerating in recent decades. We find a significant role for both climate change and whaling in restructuring communities, identifying unique variance in whole-community change explained by each driver. Moreover, we find a negative association between whaling and metazoan families which feed from the water column, suggesting that pre-whaling ecosystems had greater pelagic productivity. Overall, our results reveal baseline Antarctic biodiversity from long before observational records and identify a distinct fingerprint of human drivers in this fragile, rapidly changing ecosystem.

ecology↗

bioRxiv2026

Primary cilia coordinate c-KIT signaling induced proliferation in alpha cells

Circulating glucagon levels are elevated in patients with diabetes and obesity and contribute to hyperglycemia. The mechanisms underlying hyperglucagonemia remain poorly understood, but expansion of pancreatic -cell mass is thought to play an important role. Primary cilia are sensory organelles that act as signaling hubs, for pathways controlling cell differentiation, proliferation, and function, yet their contribution to -cell biology remains poorly defined. Here we investigated the role of primary cilia in the regulation of -cell proliferation. To this end we generated the first -cell primary cilia proteome identifying 167 cilia-enriched proteins. Among these, we identified and validated the proto-oncogene receptor tyrosine kinase, c-KIT, as a novel ciliary receptor in -cells. We further show that c-KIT signaling depends on intact primary cilia and that stimulation of isolated mouse islets with its endogenous ligand, stem cell factor (SCF), promotes -cell proliferation. In human pancreatic islets KITLG mRNA expression, but not KIT mRNA expression, correlated positively with donor BMI, suggesting that increased ligand availability drives c-KIT signaling in obesity. Together, our findings identify the primary cilium as a signaling platform c-KIT in cells and reveal a ciliary axis that may drive -cell expansion and hyperglucagonemia in obesity and diabetes.

physiology↗

bioRxiv2026

Analysis of motor-based transport in primary cilia by dynamic mode decomposition of live-cell imaging data

Kinesin-3 motor proteins are increasingly recognized for their important roles in cilia. The mammalian kinesin-3 motor KIF13B moves bidirectionally in primary cilia and regulates ciliary content, but its relationship to the intraflagellar transport (IFT) machinery is unclear. Here, we combine quantitative live-cell imaging with a new kymograph analysis based on dynamic mode decomposition (DMD) to separate mobile from immobile protein populations in primary cilia. This approach simplifies extraction of molecular velocities from kymographs and reveals that a KIF13B deletion mutant retaining only the motor domain and part of the forkhead-associated domain does not alter steady-state IFT velocity or frequency. However, when retrograde dynein-2 function is inhibited by Ciliobrevin D, both anterograde and retrograde IFT velocities decrease in parental cells, as expected, but remain unchanged in KIF13B mutant cells. Structured illumination, confocal, and STED microscopy further show that KIF13B localizes to the ciliary membrane and concentrates at the periciliary membrane region and the centriolar subdistal appendages, below the distal appendage marker FBF1. Our improved kymograph approach provides new insight into KIF13B ciliary function and simplifies the quantitative analysis of ciliary protein transport.

biophysics↗

bioRxiv2026

NBCn1 interacts with DYNLL1 and regulates ciliary length and SUFU localization to control Sonic hedgehog signaling

Primary cilia integrate morphogen signaling with cellular physiology, yet how ion transporters contribute to ciliary organization and function remains poorly understood. Here, we identify the sodium-bicarbonate cotransporter NBCn1 (SLC4A7) as a previously unrecognized ciliary membrane component essential for regulating ciliary length and Sonic hedgehog (Shh) signaling. NBCn1 localizes to primary cilia through distinct Nand Cterminal targeting motifs and inhibition of dynein activity or loss of DLG1, a known NBCn1 interacting protein, augments its ciliary localization. Loss of NBCn1 shortens cilia without altering ciliation frequency or deciliation kinetics, indicating a selective role in ciliary elongation control rather than in ciliogenesis initiation or maintenance. NBCn1 deficiency or -inhibition leads to ciliary enrichment of SUFU even at basal level and markedly attenuates GLI1 transcriptional activation, despite intact SMO ciliary entry. Structural modeling and coimmunoprecipitation reveal that NBCn1 interacts with DYNLL1, VPS45, and the transitionzone protein TMEM216, suggesting that NBCn1 modulates ciliary length and Shh signaling through interactions with these proteins. Together, these findings uncover NBCn1 as a central regulator of ciliary length and Shh signaling, highlighting ion transport as a critical and underappreciated determinant of ciliary signaling competence. Significance statementPrimary cilia are essential cellular signaling hubs, yet the contribution of ion transporters and pH to ciliary architecture and function has remained unclear. This study identifies the bicarbonate transporter NBCn1 as a previously unrecognized regulator of ciliary length and Sonic hedgehog (Shh) signaling. We show that NBCn1 is actively trafficked into cilia through defined Nand Cterminal determinants, is exported from cilia via retrograde intraflagellar transport (IFT), and interacts directly with IFT dynein component DYNLL1. Loss of NBCn1 selectively shortens cilia while leaving ciliogenesis frequency and deciliation dynamics intact. NBCn1 deficiency disrupts the ciliary localization of the key Shh component SUFU, leading to impaired GLI transcriptional responses. By revealing how ion transport intersects with IFT and morphogen signaling, these findings establish NBCn1 as a central integrator of ciliary microenvironmental regulation and developmental signaling output, highlighting pH regulatory ion transport as a critical and underappreciated determinant of ciliary function.

cell biology↗

bioRxiv2026

INPP5E interactome reveals novel connections to growth factor signaling

Primary cilia are sensory cell membrane protrusions whose malfunction causes diseases known as ciliopathies. Joubert syndrome (JBTS) is a rare recessive ciliopathy causing brain malformations and kidney cysts, among other manifestations. A key player in JBTS is INPP5E, a ciliary phosphoinositide lipid phosphatase. Although INPP5E regulates ciliary growth factor signaling, the molecular mechanisms remain poorly understood. Herein, we show that a constitutively active growth factor receptor (PDGFR-D842V) stimulates INPP5E tyrosine phosphorylation, as does the SRC tyrosine kinase. INPP5E tyrosine phosphorylation did not affect its enzyme activity but was associated with stronger binding to SH3GL1, an endocytic regulator, and SNX9, a phosphoinositide-binding protein involved, like INPP5E, in growth factor-induced ciliary ectovesicle release. Our INPP5E interactomic studies identified other growth factor signaling regulators, including among others: SIN1 (the phosphoinositide-binding subunit of the mTORC2 complex), STRAP (a TGF{beta} and PI3K/AKT signaling regulator), GRB2 (a growth factor receptor adaptor) and the JBTS-associated proteins AHI1 and NPHP1. Moreover, INPP5E strongly interacted with the phosphopeptide-binding 14-3-3 proteins, and did so only in presence of serine-85, a phosphorylated INPP5E residue. Lastly, we found that INPP5E differentially regulates two cilium-dependent growth factor signaling pathways in fibroblasts. Thus, while INPP5E downregulated PDGF-induced AKT phosphorylations, it upregulated TGF{beta}-induced SMAD2 and ERK phosphorylations. Altogether, our work provides important clues on the cilia-dependent actions of growth factors, with implications for ciliopathies like JBTS.

biochemistry↗

bioRxiv2025

CAKUT variants in PRPF8, DYRK2, and CEP78: implications for splicing and ciliogenesis

IntroductionCongenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease in children and young adults. Although over 50 monogenic causes have been identified, many remain unresolved. PRPF8 is a core spliceosome component, essential for pre-mRNA splicing, and further localizes to the distal mother centriole to promote ciliogenesis. MethodsWe performed trio exome sequencing in 208 CAKUT families and identified strong variants in PRPF8 and the EDD-DYRK2-DDB1VprBP complex. Functional validation included splicing assays in yeast (Saccharomyces cerevisiae), Sonic hedgehog (Shh) signaling in RPE-1 cells, co-immunoprecipitation for protein complex assembly, and in situ hybridization in mouse embryos. Protein interactions were modeled using AlphaFold. ResultsWe identified heterozygous de novo or inherited variants in PRPF8, DYRK2, DDB1, EDD and CEP78. Yeast assays revealed that while most PRPF8 variants preserved growth and splicing at consensus splice sites, the de novo PRPF8R1681W variant impaired splicing of non-consensus splice sites and was inviable at elevated temperature. CAKUT variants failed to rescue prp28-1 and U4-cs1 alleles but showed variant-specific synthetic interactions with brr2-1, including weak suppression or synthetic sickness at elevated temperatures. Shh signaling was reduced in [~]50% of PRPF8 variants expressed in RPE-1 cells. CEP78 truncating variants abrogated binding to CEP350 and VPRBP. Two DYRK2 variants disrupted EDD-DYRK2-DDB1VprBP complex formation without affecting kinase activity. In situ hybridization revealed strong Prpf8 expression in the developing collecting duct and urothelium. ConclusionVariants in PRPF8 and components of the EDD-DYRK2-DDB1VprBP complex may contribute to CAKUT through impaired pre-mRNA splicing and defective ciliogenesis. These findings uncover an entirely new functional network of candidate genes for CAKUT and ciliopathies, significantly broadening our understanding of disease mechanisms and offering novel entry points for mechanistic studies. Translational StatementOur study identifies a previously unrecognized molecular network involving PRPF8 and the EDD-DYRK2-DDB1VprBP complex, revealing a novel pathogenic mechanism in CAKUT. These results introduce a new class of candidate genes and pathways essential for kidney development. As the genetic etiology of CAKUT remains unknown in most patients, our findings underscore the need for targeted genetic testing and functional studies to enhance diagnosis, advance mechanistic insight, and enable more personalized clinical management.

genetics↗

bioRxiv2024

Ancient environmental DNA indicates limited human impact on marine biodiversity in pre-industrial Iceland

Human activities are affecting marine biodiversity globally by accelerating extinction rates, altering ecosystem conditions, and changing community structures. These changes can only be understood through establishing the ecosystem state prior to significant anthropogenic impact, and by disentangling the anthropogenic effect from natural climatic changes. Here, we reconstruct marine biodiversity in Iceland across three millennia (1315 BCE-1785 CE), encompassing periods of climatic fluctuation and human settlement, to explore the comparative effect of natural and anthropogenic forces on marine biodiversity. We performed 18S metabarcoding of ancient environmental DNA from two sediment cores collected from northern Icelandic shelf seas, integrating local climatic records, population estimates and zooarchaeological remains from published sources to estimate the influence of climatic and anthropogenic impacts. Against the backdrop of increasing human populations and marine exploitation, we observe no large-scale taxonomic shifts or anthropogenic biodiversity changes across the period. In contrast, we found a positive correlation between herring (Clupea harengus) detection rates and proxy-reconstructed sea surface temperature, suggesting a role for climate in shaping marine biodiversity. Overall, our data suggest that despite impacts on terrestrial ecosystems and the development of a substantial export fishery across the study period, Icelandic society may have had a limited effect on marine biodiversity.

ecology↗

bioRxiv2024

TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development

Transforming Growth Factor-Beta-Activated Kinase 1 (TAK1/MAP3K7), along with its upstream regulators TAK1-Binding Protein 2 (TAB2) and the catalytic alpha-subunit of Protein Kinase A (PKA-C/PRKACA), has been identified as a pivotal player in regulation of developmental processes. Haploinsufficiency of TAB2 causes Congenital Heart Disease (CHD) and rare variants in PKA-C and TAK1 cause cardioacrofacial dysplasia (CAFD), and Frontometaphyseal Dysplasia (FMD) and cardiospondylocarpofacial syndrome (CSCFS), respectively, rare multisystem syndromes, where CHD may appear in the clinical spectrum. We hypothesized that TAK1 plays a significant role in heart development and CHD and addressed this by genetic analysis in CHD patient cohorts and experiments in cell and animal models. Exome sequencing data from 1,471 CHD patients with extracardiac anomalies (syndromic CHD, sCHD), 2,405 patients with nonsyndromic CHD (nsCHD) and 45,082 controls showed increased burden of rare TAB2 and TAK1 variants in sCHD, but not in nsCHD. Detailed characterization of tak1-/-and tab2-/- zebrafish mutants revealed cardiac defects (dilated atrium, trabeculation defects, tachycardia and reduced contractility) as well as extracardiac developmental anomalies. RNA sequencing of tak1-/- mutant hearts showed downregulation of genes encoding core cardiac transcription factors, sarcomeric proteins and extracellular matrix proteins. Experiments with cell cultures and analysis of zebrafish larvae and gastruloids indicated that TAK1 via TAB2 and PKA-C is activated at the primary cilium during cardiomyogenesis and that TAK1 activation at this site is enhanced by cardiomyogenic signaling molecules, including ligands of the TGFB/BMP superfamily. Consistent with these findings, CRISPR/Cas9-mediated editing of TAK1 or administration of small molecule inhibitors targeting TAK1 inhibited ciliary signaling and cardiomyocyte differentiation in vitro, while FMD-causing mutations in TAK1 reduced its ciliary localization. In conclusion, our data establishes a central role for TAK1 and its upstream regulators in cardiac development and syndromic CHD, coordinated via the primary cilium.

developmental biology↗

bioRxiv2024

Loss of KIF13B causes time-dependent changes in ciliary polycystin-2 levels and extracellular vesicle release

Dynamic control of ciliary membrane protein content is crucial for the organelles homeostasis and signaling function and involves removal of ciliary components by BBSome-mediated export, endocytic retrieval and/or extracellular vesicle (EV) shedding. We report that KIF13B regulates ciliary protein composition and EV shedding in cultured kidney epithelial cells, with effects that vary over time. In early stages of ciliation Kif13b-/- cells aberrantly accumulate PC2, FLOT1, and HGS within cilia. These cells also produce fewer small EVs through the GW4869-sensitive, nSMase2 pathway, and release large EVs enriched with CCDC198 and the centriole distal appendage protein CCDC92, which also localizes to the ciliary tip. Upon cilia maturation, Kif13b-/- cells accelerate large EV release of numerous ciliary proteins, including PC2, BBSome components, and IFT proteins, which correlates with gradual depletion of CCDC92 and PC2 from the ciliary tip and shaft, respectively. Furthermore, over time, Kif13b-/- cells show an upregulation in the release of small EVs, which differ in composition from wild-type small EVs. Specifically, the mutant small EVs lack several proteins that are enriched in small EVs from BBSome-deficient cells, such as the palmitoyl transferase ZDHHC5, which localizes to cilia, accumulates within cilia of BBSome-deficient cells, and regulates ciliary length and PC2 levels. Collectively, our work suggests that KIF13B acts at the level of centriole distal appendages to limit ciliary protein entrance and promote endocytic retrieval downstream of the BBSome. Furthermore, this study shows for the first time that CCDC198 and ZDHHC5 localize to primary cilia, suggesting they are potential novel ciliopathy candidates.

cell biology↗

bioRxiv2023

DLG1 functions upstream of SDCCAG3 and IFT20 to control targeting of polycystin-2 to the primary cilium

Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney caused ciliary elongation and cystogenesis, and cell-based proximity labelling proteomics and fluorescence microscopy showed alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20 and polycystin-2 (PC2) were reduced in cilia of DLG1 deficient cells compared to control cells. This phenotype was recapitulated in vivo and rescuable by re-expression of wildtype DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggested that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.

cell biology↗

bioRxiv2021

Angiomotin isoform 2 promotes binding of PALS1 to KIF13B at the base of primary cilia and suppresses ciliary elongation

The kinesin-3 motor KIF13B functions in endocytosis, vesicle transport, and regulation of ciliary length and signaling. Direct binding of the membrane-associated guanylate kinase (MAGUK) DLG1 to KIF13Bs MAGUK-binding stalk (MBS) domain relieves motor autoinhibition and promotes microtubule plus end-directed cargo transport. Here we characterize Angiomotin isoform 2 (Ap80) as a novel KIF13B interactor that promotes binding of another MAGUK, the polarity protein and Crumbs complex component PALS1, to KIF13B. Live cell imaging analysis indicated that Ap80 is concentrated at the base of primary cilia and recruits PALS1 to this site, but is not itself a cargo of KIF13B. Consistent with a ciliary function for Ap80, its depletion led to elongated primary cilia while its overexpression caused ciliary shortening. Our results suggest that Ap80 may specifically activate KIF13B cargo binding at the base of primary cilia to regulate ciliary length.

cell biology↗

bioRxiv2021

Transient accumulation and bidirectional movement of KIF13B in primary cilia

Primary cilia are microtubule-based sensory organelles whose assembly and function rely on the conserved bidirectional intraflagellar transport (IFT) system, which is powered by anterograde kinesin-2 and retrograde cytoplasmic dynein 2 motors. Nematodes additionally employ a cell type-specific kinesin-3 motor, KLP-6, which moves within cilia independently of IFT and regulates ciliary content and function. Here we provide evidence that a KLP-6 homolog, KIF13B, undergoes bursts of bidirectional movement within primary cilia of cultured immortalized human retinal pigment epithelial (hTERT-RPE1) cells. Anterograde and retrograde intraciliary velocities of KIF13B were similar to those of IFT (IFT172-eGFP), but intraciliary movement of KIF13B required its own motor domain and appeared to be cell-type specific. Our work provides the first demonstration of motor-driven, intraciliary movement by a vertebrate kinesin other than kinesin-2 motors.

biophysics↗

bioRxiv2020

Detecting flying insects using mega-nets and meta-barcoding

Insect diversity and abundance are increasingly reported as being under pressure. However, monitoring insects across space and time is challenging, due to their vast taxonomic and functional diversity. This study demonstrates how nets mounted on rooftops of cars (car nets) and DNA metabarcoding can be applied to sample flying insect diversity across a large spatial scale within a limited time period. During June 2018, 365 car net samples were collected by 151 volunteers during two daily time intervals on 218 routes in Denmark. Insect bulk samples were processed with a DNA metabarcoding protocol to estimate taxonomic composition, and the results were compared to known flying insect diversity and occurrence data. We detected 15 out of 19 flying insect orders present in Denmark. Diptera. Psocoptera and Thysanoptera were overrepresented, while Hymenoptera, Coleoptera, Lepidoptera, Trichoptera, Odonata, Neuroptera and Plecoptera were underrepresented, compared to Danish estimates. We detected 319 species not known for Denmark. Our results indicate that this method can assess the flying insect fauna to a wide extent, but may be, like other methods, biased towards certain insect orders. Furthermore, car net sampling and DNA metabarcoding can update species records for Denmark while preserving specimens for natural history collections.

ecology↗

bioRxiv2020

CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels

CEP78 is a centrosomal protein implicated in ciliogenesis and ciliary length control, and mutations in the CEP78 gene cause retinal cone-rod dystrophy associated with hearing loss. However, the mechanism by which CEP78 affects cilia formation is unknown. Based on a recently discovered disease-causing CEP78 p.L150S mutation, we identified the disease-relevant interactome of CEP78. We confirmed that CEP78 interacts with the EDD1-DYRK2-DDB1VPRBP E3 ubiquitin ligase complex, which is involved in CP110 ubiquitination and degradation, and identified a novel interaction between CEP78 and CEP350 that is weakened by the CEP78L150S mutation. We show that CEP350 promotes centrosomal recruitment and stability of CEP78, which in turn leads to centrosomal recruitment of EDD1. Consistently, cells lacking CEP78 display significantly increased cellular and centrosomal levels of CP110, and depletion of CP110 in CEP78-deficient cells restored ciliation frequency to normal. We propose that CEP78 functions downstream of CEP350 to promote ciliogenesis by negatively regulating CP110 levels via an EDD1-dependent mechanism.

cell biology↗

bioRxiv2020

Contrasting impacts of urban and farmland cover on flying insect biomass

Recent studies report declines in biomass, abundance and diversity of terrestrial insect groups. While anthropogenic land use is one likely contributor to this decline, studies assessing land cover as a driver of insect dynamics are rare and mostly restricted in spatial scale and types of land cover. In this study, we used rooftop-mounted car nets in a citizen science project ( InsectMobile) to allow for large-scale geographic sampling of flying insects across Denmark and parts of Germany. Citizen scientists sampled insects along 278 10 km routes in urban, farmland and semi-natural (grassland, wetland and forest) landscapes in the summer of 2018. We assessed the importance of local to landscape-scale effects and land use intensity by relating insect biomass to land cover in buffers of 50, 250, 500 and 1000 m along the routes. We found a negative association of urban cover and a positive association of farmland on insect biomass at a landscape-scale (1000 m buffer) in both countries. In Denmark, we also found positive effects of all semi-natural land covers, i.e. grassland (largest at the landscape-scale, 1000 m), forests (largest at intermediate scales, 250 m), and wetlands (largest at the local-scale, 50 m). The negative association of insect biomass with urban land cover and positive association with farmland were not clearly modified by any variable associated with land use intensity. Our results show that land cover has an impact on flying insect biomass with the magnitude of this effect varying across spatial scales. Since we consistently found negative effects of urban land cover, our findings highlight the need for the conservation of semi-natural areas, such as wetlands, grasslands and forests, in Europe.

ecology↗

bioRxiv2020

Concerted action of kinesin-1 KIF5B and kinesin-3 KIF13B promotes efficient transport of exocytotic vesicles to microtubule plus ends

Intracellular transport relies on multiple kinesins, but it is poorly understood which kinesins are present on particular cargos, what their contributions are and whether they act simultaneously on the same cargo. Here, we show that Rab6-positive secretory vesicles are transported from the Golgi apparatus to the cell periphery by kinesin-1 KIF5B and kinesin-3 KIF13B, which determine the location of secretion events. KIF5B plays a dominant role, whereas KIF13B helps Rab6 vesicles to reach freshly polymerized microtubule ends, to which KIF5B binds poorly, likely because its cofactors, MAP7-family proteins, are slow in populating these ends. Sub-pixel localization demonstrated that during microtubule plus-end directed transport, both kinesins localize to the vesicle front and can be engaged on the same vesicle. When vesicles reverse direction, KIF13B relocates to the middle of the vesicle, while KIF5B shifts to the back, suggesting that KIF5B but not KIF13B undergoes a tug-of-war with a minus-end directed motor.

cell biology↗

bioRxiv2019

RRP7A links primary microcephaly to radial glial cells and dysfunction of ribosomal biogenesis, neurogenesis and ciliary resorption

Introductory paragraphPrimary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability1. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role1. Using homozygosity mapping and whole exome sequencing, we identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, which segregated with MCPH in a consanguineous family with 10 affected individuals. RRP7A is expressed in neural stem cells/radial glial cells of the developing human forebrain, and targeted mutation of Rrp7a leads to defects in both neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in processing of ribosomal RNA, resorption of primary cilia and cell cycle progression. Finally, analysis of zebrafish embryos with loss-of-function mutation in rrp7a confirmed that RRP7A depletion causes reduced brain size, impaired neurogenesis and cell proliferation as well as defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.

neuroscience↗

bioRxiv2018

MobiSeq: De Novo SNP discovery in model and non-model species through sequencing the flanking region of transposable elements

In recent years, the availability of reduced representation library (RRL) methods has catalysed an expansion of genome-scale studies to characterize both model and non-model organisms. Most of these methods rely on the use of restriction enzymes to obtain DNA sequences at a genome-wide level. These approaches have been widely used to sequence thousands of markers across individuals for many organisms at a reasonable cost, revolutionizing the field of population genomics. However, there are still some limitations associated with these methods, in particular, the high molecular weight DNA required as starting material, the reduced number of common loci among investigated samples, and the short length of the sequenced site-associated DNA. Here, we present MobiSeq, a RRL protocol exploiting simple laboratory techniques, that generates genomic data based on PCR targeted-enrichment of transposable elements and the sequencing of the associated flanking region. We validate its performance across 103 DNA extracts derived from three mammalian species: grey wolf (Canis lupus), red deer complex (Cervus sp.), and brown rat (Rattus norvegicus). MobiSeq enables the sequencing of hundreds of thousands loci across the genome, and performs SNP discovery with relatively low rates of clonality. Given the ease and flexibility of MobiSeq protocol, the method has the potential to be implemented for marker discovery and population genomics across a wide range of organisms - enabling the exploration of diverse evolutionary and conservation questions.

genomics↗