bims-bicyki 2023-07-30 papers

bims-bicyki

Biomed News

on Bicaudal-C1 and interactors in cystic kidney disease

Issue of 2023‒07‒30
thirteen papers selected by
Céline Gagnieux
École Polytechnique Fédérale de Lausanne (EPFL)

Assessment of metabolic risk factors for nephrolithiasis in patients with autosomal dominant polycystic kidney disease: a cross-sectional study.
Cilia and Cancer: From Molecular Genetics to Therapeutic Strategies.
Efficacy of beetroot juice on reducing blood pressure in hypertensive adults with autosomal dominant polycystic kidney disease (BEET-PKD): study protocol for a double-blind, randomised, placebo-controlled trial.
Seriously cilia: A tiny organelle illuminates evolution, disease, and intercellular communication.
Large-scale epidemiological study on feline autosomal dominant polycystic kidney disease and identification of novel PKD1 gene variants.
Microstructure-Based Modeling of Primary Cilia Mechanics.
PKD1 Mutation Is a Biomarker for Autosomal Dominant Polycystic Kidney Disease.
Clinical Quality Control of MRI Total Kidney Volume Measurements in Autosomal Dominant Polycystic Kidney Disease.
Maternal protein deficiency alters primary cilia length in renal tubular and impairs kidney development in fetal rat.
Biophysical Analysis of Mechanical Signals in Immotile Cilia of Mouse Embryonic Nodes Using Advanced Microscopic Techniques.
The implication of ciliary signaling pathways for epithelial-mesenchymal transition.
Role of lipids in the control of autophagy and primary cilium signaling in neurons.
Morphological Observation and Transcriptome Analysis of Ciliogenesis in Urechis unicinctus (Annelida, Echiura).

Clin Exp Nephrol. 2023 Jul 26.

Assessment of metabolic risk factors for nephrolithiasis in patients with autosomal dominant polycystic kidney disease: a cross-sectional study.

Onour Chasan, Safak Mirioglu, Ayse Serra Artan, Meltem Gursu, Rumeyza Kazancioglu, Omer Celal Elcioglu.

  BACKGROUND: Nephrolithiasis is more common in autosomal dominant polycystic kidney disease (ADPKD) than in the normal population. We aimed to investigate the anatomical and metabolic factors that may be associated with nephrolithiasis in patients with ADPKD METHODS: In this cross-sectional study, a total of 180 participants were included. Eighty-five patients with ADPKD [42 patients with nephrolithiasis (PKD N +) and 43 without nephrolithiasis (PKD N -)] were recruited. Forty-seven nephrolithiasis patients without ADPKD (N) and 48 healthy controls (HC) were selected as control groups. 24-h urine collections were measured in all participants. 24-h urine citrate, calcium, urate, oxalate, magnesium and sodium, serum electrolytes, and eGFRs were compared.RESULTS: Total kidney volumes were not different between patients with PKD N + and PKD N -. Hypocitraturia was common in all patients with ADPKD (69.4%), and it was not different between PKD N + (76.2%) and PKD N- (62.8%). However, hypocitraturia was statistically higher in PKD N + and PKD N - than in N (38.3%) and HC (12.5%) (p<0.05). 24-h urine calcium, urate, and oxalate levels were similar between PKD N + and PKD N - CONCLUSIONS: Hypocitraturia was found to be significantly higher in patients with ADPKD than in healthy adults and other kidney stone patients.

Keywords:  Autosomal dominant; Hypocitraturia; Nephrolithiasis; Polycystic kidney disease

DOI:  https://doi.org/10.1007/s10157-023-02378-2
Genes (Basel). 2023 Jul 11. pii: 1428. [Epub ahead of print]14(7):

Cilia and Cancer: From Molecular Genetics to Therapeutic Strategies.

Pietro Carotenuto, Sergio A Gradilone, Brunella Franco.

  Cilia are microtubule-based organelles that project from the cell surface with motility or sensory functions. Primary cilia work as antennae to sense and transduce extracellular signals. Cilia critically control proliferation by mediating cell-extrinsic signals and by regulating cell cycle entry. Recent studies have shown that primary cilia and their associated proteins also function in autophagy and genome stability, which are important players in oncogenesis. Abnormal functions of primary cilia may contribute to oncogenesis. Indeed, defective cilia can either promote or suppress cancers, depending on the cancer-initiating mutation, and the presence or absence of primary cilia is associated with specific cancer types. Together, these findings suggest that primary cilia play important, but distinct roles in different cancer types, opening up a completely new avenue of research to understand the biology and treatment of cancers. In this review, we discuss the roles of primary cilia in promoting or inhibiting oncogenesis based on the known or predicted functions of cilia and cilia-associated proteins in several key processes and related clinical implications.

Keywords:  cancer; cilia; ciliogenesis; ciliome

DOI:  https://doi.org/10.3390/genes14071428
Trials. 2023 Jul 29. 24(1): 482

Efficacy of beetroot juice on reducing blood pressure in hypertensive adults with autosomal dominant polycystic kidney disease (BEET-PKD): study protocol for a double-blind, randomised, placebo-controlled trial.

Priyanka S Sagar, Alexandra Munt, Sayanthooran Saravanabavan, Farnoosh Asghar Vahedi, James Elhindi, Beatrice Nguyen, Katrina Chau, David C Harris, Vincent Lee, Kamal Sud, Nikki Wong, Gopala K Rangan.

  BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD) impaired nitric oxide (NO) synthesis, in part, contributes to early-onset hypertension. Beetroot juice (BRJ) reduces blood pressure (BP) by increasing NO-mediated vasodilation. The aim of this double-blind, randomised, placebo-controlled study is to test the hypothesis that BRJ reduces systolic and diastolic clinic BP in hypertensive adults with ADPKD.METHODS: Participants with ADPKD and treated hypertension (n = 60) will be randomly allocated (1:1) to receive a daily dose of either nitrate-replete (400 mg nitrate/day) or nitrate-deplete BRJ for 4 weeks. The co-primary outcomes are change in mean systolic and diastolic clinic BP before and after 4 weeks of treatment with daily BRJ. Secondary outcomes are changes in daily home BP, urinary albumin to creatinine ratio, serum and salivary nitrate/nitrite levels and serum asymmetric dimethylarginine levels before and after 4 weeks of BRJ.
DISCUSSION: The effect of BRJ in ADPKD has not been previously tested. BRJ is an accessible, natural dietary supplement that, if effective, will provide a novel adjunctive approach for treating hypertension in ADPKD.
TRIAL REGISTRATION: ClinicalTrials.gov NCT05401409. Retrospectively registered on 27th May 2022.

Keywords:  Beetroot juice; Dietary interventions in hypertension; Polycystic kidney disease

DOI:  https://doi.org/10.1186/s13063-023-07519-2
Dev Cell. 2023 Jul 20. pii: S1534-5807(23)00325-8. [Epub ahead of print]

Seriously cilia: A tiny organelle illuminates evolution, disease, and intercellular communication.

Camille Derderian, Gabriela I Canales, Jeremy F Reiter.

  The borders between cell and developmental biology, which have always been permeable, have largely dissolved. One manifestation is the blossoming of cilia biology, with cell and developmental approaches (increasingly complemented by human genetics, structural insights, and computational analysis) fruitfully advancing understanding of this fascinating, multifunctional organelle. The last eukaryotic common ancestor probably possessed a motile cilium, providing evolution with ample opportunity to adapt cilia to many jobs. Over the last decades, we have learned how non-motile, primary cilia play important roles in intercellular communication. Reflecting their diverse motility and signaling functions, compromised cilia cause a diverse range of diseases collectively called "ciliopathies." In this review, we highlight how cilia signal, focusing on how second messengers generated in cilia convey distinct information; how cilia are a potential source of signals to other cells; how evolution may have shaped ciliary function; and how cilia research may address thorny outstanding questions.

Keywords:  ADPKD; BBSome; Foxj1; Hedgehog; LECA; PKA; PKD; cAMP; ciliation; ciliogenesis; polycystic; transition zone

DOI:  https://doi.org/10.1016/j.devcel.2023.06.013
J Feline Med Surg. 2023 Jul;25(7): 1098612X231185393

Large-scale epidemiological study on feline autosomal dominant polycystic kidney disease and identification of novel PKD1 gene variants.

Fumitaka Shitamori, Ayaka Nonogaki, Tomoki Motegi, Yuki Matsumoto, Mika Sakamoto, Yasuhiro Tanizawa, Yasukazu Nakamura, Tomohiro Yonezawa, Yasuyuki Momoi, Shingo Maeda.

  OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease in cats. In most cases, the responsible abnormality is a nonsense single nucleotide polymorphism in exon 29 of the PKD1 gene (chrE3:g.42858112C>A, the conventional PKD1 variant). The aim of this study was to conduct a large-scale epidemiological study of ADPKD caused by the conventional PKD1 variant in Japan and to search for novel polymorphisms by targeted resequencing of the PKD1 using a next-generation sequencer.METHODS: A total of 1281 cats visiting the Veterinary Medical Center of the University of Tokyo were included in this study. DNA was extracted from the blood of each cat. We established a novel TaqMan real-time PCR genotyping assay for the conventional PKD1 variant, and all cases were examined for the presence of this variant. Targeted resequencing of all exons of the PKD1 was performed on the DNA of 23 cats with the conventional PKD1 variant, six cats diagnosed with cystic kidneys but without this variant, and 61 wild-type normal cats.
RESULTS: Among the 1281 cats examined in this study, 23 (1.8%) harboured the conventional PKD1 variant. The odds of having the conventional PKD1 variant were significantly higher in Persian cats, Scottish Folds and Exotic Shorthairs than in the other breeds, although the number of cases in each breed was small. Furthermore, we identified four variants unique to cats with cystic kidneys that were not found in wild-type normal cats, all of which were in exon 15. In particular, two (chrE:g.42848725delC, pGly1641fs and chrE:g.42850283C>T, pArg2162Trp) were candidate variants.
CONCLUSIONS AND RELEVANCE: This study revealed that the conventional PKD1 variant was prevalent in Scottish Fold, Persian and Exotic Shorthair breeds in Japan, and variants in exon 15 of PKD1, in addition to the conventional variant in exon 29, would be key factors in the pathogenesis of ADPKD in cats.

Keywords:  Autosomal dominant polycystic kidney disease; epidemiology; genotyping; target resequencing

DOI:  https://doi.org/10.1177/1098612X231185393
bioRxiv. 2023 Jul 15. pii: 2023.07.14.549117. [Epub ahead of print]

Microstructure-Based Modeling of Primary Cilia Mechanics.

Nima Mostafazadeh, Andrew Resnick, Y-N Young, Zhangli Peng.

A primary cilium, made of nine microtubule doublets enclosed in a cilium membrane, is a mechanosensing organelle that bends under an external mechanical load and sends an intracellular signal through transmembrane proteins activated by cilium bending. The nine microtubule doublets are the main load-bearing structural component, while the transmembrane proteins on the cilium membrane are the main sensing component. No distinction was made between these two components in all existing models, where the stress calculated from the structural component (nine microtubule doublets) was used to explain the sensing location, which may be totally misleading. For the first time, we developed a microstructure-based primary cilium model by considering these two components separately. First, we refined the analytical solution of bending an orthotropic cylindrical shell for individual microtubule, and obtained excellent agreement between finite element simulations and the theoretical predictions of a microtubule bending as a validation of the structural component in the model. Second, by integrating the cilium membrane with nine microtubule doublets, we found that the microtubule doublets may twist significantly as the whole cilium bends. Third, besides being cilium-length-dependent, we found the mechanical properties of the cilium are also highly deformation-dependent. More important, we found that the cilium membrane near the base is not under pure in-plane tension or compression as previously thought, but has significant local bending stress. This challenges the traditional model of cilium mechanosensing, indicating that transmembrane proteins may be activated more by membrane curvature than membrane stretching. Finally, we incorporated imaging data of primary cilia into our microstructure-based cilium model, and found that comparing to the ideal model with uniform microtubule length, the imaging-informed model shows the nine microtubule doublets interact more evenly with the cilium membrane, and their contact locations can cause even higher bending curvature in the cilium membrane than near the base.SIGNIFICANCE: Factors regulating the mechanical response of a primary cilium to fluid flow remain unclear. Modeling the microtubule doublet as a composite of two orthotropic shells and the ciliary axoneme as an elastic shell enclosing nine such microtubule doublets, we found that the length distribution of microtubule doublets (inferred from cryogenic electron tomography images) is the primary determining factor in the bending stiffness of primary cilia, rather than just the ciliary length. This implies ciliary-associated transmembrane proteins may be activated by membrane curvature changes rather than just membrane stretching. These insights challenge the traditional view of ciliary mechanosensation and expands our understanding of the different ways in which cells perceive and respond to mechanical stimuli.

DOI: https://doi.org/10.1101/2023.07.14.549117
Biomolecules. 2023 Jun 21. pii: 1020. [Epub ahead of print]13(7):

PKD1 Mutation Is a Biomarker for Autosomal Dominant Polycystic Kidney Disease.

Tomoki Kimura, Haruna Kawano, Satoru Muto, Nobuhito Muramoto, Toshiaki Takano, Yan Lu, Hidetaka Eguchi, Hiroo Wada, Yasushi Okazaki, Hisamitsu Ide, Shigeo Horie.

  BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1 in 500-4000 people worldwide. Genetic mutation is a biomarker for predicting renal dysfunction in patients with ADPKD. In this study, we performed a genetic analysis of Japanese patients with ADPKD to investigate the prognostic utility of genetic mutations in predicting renal function outcomes.METHODS: Patients clinically diagnosed with ADPKD underwent a panel genetic test for germline mutations in PKD1 and PKD2. This study was conducted with the approval of the Ethics Committee of Juntendo University (no. 2019107).
RESULTS: Of 436 patients, 366 (83.9%) had genetic mutations. Notably, patients with PKD1 mutation had a significantly decreased ΔeGFR/year compared to patients with PKD2 mutation, indicating a progression of renal dysfunction (-3.50 vs. -2.04 mL/min/1.73 m2/year, p = 0.066). Furthermore, PKD1 truncated mutations had a significantly decreased ΔeGFR/year compared to PKD1 non-truncated mutations in the population aged over 65 years (-6.56 vs. -2.16 mL/min/1.73 m2/year, p = 0.049). Multivariate analysis showed that PKD1 mutation was a more significant risk factor than PKD2 mutation (odds ratio, 1.81; 95% confidence interval, 1.11-3.16; p = 0.020).
CONCLUSIONS: The analysis of germline mutations can predict renal prognosis in Japanese patients with ADPKD, and PKD1 mutation is a biomarker of ADPKD.

Keywords:  ADPKD; PKD1 mutation; analysis of germline mutations; biomarkers; predicting renal prognosis

DOI:  https://doi.org/10.3390/biom13071020
Tomography. 2023 07 12. 9(4): 1341-1355

Clinical Quality Control of MRI Total Kidney Volume Measurements in Autosomal Dominant Polycystic Kidney Disease.

Chenglin Zhu, Hreedi Dev, Arman Sharbatdaran, Xinzi He, Daniil Shimonov, James M Chevalier, Jon D Blumenfeld, Yi Wang, Kurt Teichman, George Shih, Akshay Goel, Martin R Prince.

  Total kidney volume measured on MRI is an important biomarker for assessing the progression of autosomal dominant polycystic kidney disease and response to treatment. However, we have noticed that there can be substantial differences in the kidney volume measurements obtained from the various pulse sequences commonly included in an MRI exam. Here we examine kidney volume measurement variability among five commonly acquired MRI pulse sequences in abdominal MRI exams in 105 patients with ADPKD. Right and left kidney volumes were independently measured by three expert observers using model-assisted segmentation for axial T2, coronal T2, axial single-shot fast spin echo (SSFP), coronal SSFP, and axial 3D T1 images obtained on a single MRI from ADPKD patients. Outlier measurements were analyzed for data acquisition errors. Most of the outlier values (88%) were due to breathing during scanning causing slice misregistration with gaps or duplication of imaging slices (n = 35), slice misregistration from using multiple breath holds during acquisition (n = 25), composing of two overlapping acquisitions (n = 17), or kidneys not entirely within the field of view (n = 4). After excluding outlier measurements, the coefficient of variation among the five measurements decreased from 4.6% pre to 3.2%. Compared to the average of all sequences without errors, TKV measured on axial and coronal T2 weighted imaging were 1.2% and 1.8% greater, axial SSFP was 0.4% greater, coronal SSFP was 1.7% lower and axial T1 was 1.5% lower than the mean, indicating intrinsic measurement biases related to the different MRI contrast mechanisms. In conclusion, MRI data acquisition errors are common but can be identified using outlier analysis and excluded to improve organ volume measurement consistency. Bias toward larger volume measurements on T2 sequences and smaller volumes on axial T1 sequences can also be mitigated by averaging data from all error-free sequences acquired.

Keywords:  ADPKD; MRI; T1; T2; outlier analysis; quality control; steady state free precession; total kidney volume

DOI:  https://doi.org/10.3390/tomography9040107
Front Nutr. 2023 ;10 1156029

Maternal protein deficiency alters primary cilia length in renal tubular and impairs kidney development in fetal rat.

Jun Wang, Pei Zhou, Liangliang Zhu, Hongbo Guan, Jian Gou, Xiaomei Liu.

  Introduction: Intrauterine malnutrition impairs embryo kidney development and leads to kidney disease and hypertension in adulthood, yet the underlying mechanism remains unclear.Methods: With a maternal protein restriction (MPR) rat model, we investigated the critical ciliogenesis factors and β-catenin pathway in FGR fetal kidneys and analyzed the impact of aberrant primary cilia on renal tubular epithelium.
Results: The data showed decreased nephron number and renal tubular dysgenesis in FGR fetus. FGR fetus showed deregulated expression of ciliogenesis factors including upregulation of IFT88 and downregulation of DYNLT1, accompanied with cilia elongation in renal tubular epithelial cells. Wnt7b, the key ligand for Wnt/β-catenin signaling, was downregulated and nuclear translocation of β-catenin was decreased. The proapoptotic protein was upregulated. In vitro study with HK-2 cells showed that overexpression of IFT88 lengthened the cilia, inhibited β-catenin signaling. Besides, IFT88 overexpression suppressed cell proliferation, activated autophagy, and induced cell apoptosis. Inhibition of autophagy partly restored the cilia length and cell viability. Likewise, knockdown of DYNLT1 led to cilia elongation, suppressed cell proliferation, and promoted apoptosis in HK-2 cell. However, the cilia elongation induced by DYNLT1 knockdown was not autophagy-dependent, but associated with reactive oxygen species (ROS) accumulation.
Discussion: We elucidated that intrauterine protein malnutrition led to deregulation of ciliogenesis factors and cilia elongation in renal tubular epithelial, inhibited β-catenin signaling, and induced cell apoptosis and ultimately, compromised kidney development.

Keywords:  DYNLT1; FGR; IFT88; kidney; primary cilia; β-catenin pathway

DOI:  https://doi.org/10.3389/fnut.2023.1156029
Bio Protoc. 2023 Jul 20. 13(14): e4715

Biophysical Analysis of Mechanical Signals in Immotile Cilia of Mouse Embryonic Nodes Using Advanced Microscopic Techniques.

Takanobu A Katoh, Toshihiro Omori, Takuji Ishikawa, Yasushi Okada, Hiroshi Hamada.

  Immotile cilia of crown cells at the node of mouse embryos are required for sensing leftward fluid flow that gives rise to the breaking of left-right (L-R) symmetry. The flow-sensing mechanism has long remained elusive, mainly because of difficulties inherent in manipulating and precisely analyzing the cilium. Recent progress in optical microscopy and biophysical analysis has allowed us to study the mechanical signals involving primary cilia. In this study, we used high-resolution imaging with mechanical modeling to assess the membrane tension in a single cilium. Optical tweezers, a technique used to trap sub-micron-sized particles with a highly focused laser beam, allowed us to manipulate individual cilia. Super-resolution microscopy allowed us to discern the precise localization of ciliary proteins. Using this protocol, we provide a method for applying these techniques to cilia in mouse embryonic nodes. This method is widely applicable to the determination of mechanical signals in other cilia.

Keywords:  Left-right symmetry breaking; Mathematical modeling; Mechanical Simulation; Optical tweezers; Super-resolution imaging; mRNA imaging

DOI:  https://doi.org/10.21769/BioProtoc.4715
Mol Cell Biochem. 2023 Jul 25.

The implication of ciliary signaling pathways for epithelial-mesenchymal transition.

Bang-Hua Zhong, Ming Dong.

  Epithelial-to-mesenchymal transition (EMT), which plays an essential role in development, tissue repair and fibrosis, and cancer progression, is a reversible cellular program that converts epithelial cells to mesenchymal cell states characterized by motility-invasive properties. The mostly signaling pathways that initiated and controlled the EMT program are regulated by a solitary, non-motile organelle named primary cilium. Acting as a signaling nexus, primary cilium dynamically concentrates signaling molecules to respond to extracellular cues. Recent research has provided direct evidence of connection between EMT and primary ciliogenesis in multiple contexts, but the mechanistic understanding of this relationship is complicated and still undergoing. In this review, we describe the current knowledge about the ciliary signaling pathways involved in EMT and list the direct evidence that shows the link between them, trying to figure out the intricate relationship between EMT and primary ciliogenesis, which may aid the future development of primary cilium as a novel therapeutic approach targeted to EMT.

Keywords:  Cancer; Ciliogenesis; EMT; Primary cilium; Signaling pathway

DOI:  https://doi.org/10.1007/s11010-023-04817-w
Neural Regen Res. 2024 Feb;19(2): 264-271

Role of lipids in the control of autophagy and primary cilium signaling in neurons.

María Paz Hernández-Cáceres, Daniela Pinto-Nuñez, Patricia Rivera, Paulina Burgos, Francisco Díaz-Castro, Alfredo Criollo, Maria Jose Yañez, Eugenia Morselli.

  The brain is, after the adipose tissue, the organ with the greatest amount of lipids and diversity in their composition in the human body. In neurons, lipids are involved in signaling pathways controlling autophagy, a lysosome-dependent catabolic process essential for the maintenance of neuronal homeostasis and the function of the primary cilium, a cellular antenna that acts as a communication hub that transfers extracellular signals into intracellular responses required for neurogenesis and brain development. A crosstalk between primary cilia and autophagy has been established; however, its role in the control of neuronal activity and homeostasis is barely known. In this review, we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in neurons. Then we review the recent literature about specific lipid subclasses in the regulation of autophagy, in the control of primary cilium structure and its dependent cellular signaling in physiological and pathological conditions, specifically focusing on neurons, an area of research that could have major implications in neurodevelopment, energy homeostasis, and neurodegeneration.

Keywords:  GPCR; NPC1; autophagic flux; cholesterol; fatty acids; lysosomal storage diseases; neurons; phosphoinositides; primary cilium

DOI:  https://doi.org/10.4103/1673-5374.377414
Int J Mol Sci. 2023 Jul 16. pii: 11537. [Epub ahead of print]24(14):

Morphological Observation and Transcriptome Analysis of Ciliogenesis in Urechis unicinctus (Annelida, Echiura).

Dexu Kong, Maokai Wei, Danwen Liu, Zhengrui Zhang, Yubin Ma, Zhifeng Zhang.

  During the early development of marine invertebrates, planktic larvae usually occur, and their body surfaces often form specific types of cilia that are involved in locomotion and feeding. The echiuran worm Urechis unicinctus sequentially undergoes the formation and disappearance of different types of body surface cilia during embryonic and larval development. The morphological characteristics and molecular mechanisms involved in the process remain unclear. In this study, we found that body surface cilia in U. unicinctus embryos and larvae can be distinguished into four types: body surface short cilia, apical tufts, circumoral cilia and telotrochs. Further, distribution and genesis of the body surface cilia were characterized using light microscope and electron microscope. To better understand the molecular mechanism during ciliogenesis, we revealed the embryonic and larval transcriptome profile of the key stages of ciliogenesis in U. unicinctus using RNA-Seq technology. A total of 29,158 differentially expressed genes (DEGs) were obtained from 24 cDNA libraries by RNA-Seq. KEGG pathway enrichment results showed that Notch, Wnt and Ca2+ signaling pathways were significantly enriched during the occurrence of apical tufts and circumoral cilia. Furthermore, all DEGs were classified according to their expression pattern, and DEGs with similar expression pattern were grouped into a module. All DEG co-expression modules were correlated with traits (body surface short cilia, apical tufts, circumoral cilia and telotrochs) by WGCNA, the results showed DEGs were divided into 13 modules by gene expression patterns and that the genes in No. 7, No. 8 and No. 10 modules were to be highly correlated with the occurrence of apical tufts, circumoral cilia and telotrochs. The top 10 hub genes in the above three modules were identified to be highly correlated with ciliogenesis, including the reported cilium-related gene Cnbd2 and unreported cilium-related candidate genes FAM181B, Capsl, Chst3, TMIE and Innexin. Notably, Innexin was included in the top10 hub genes of the two modules (No. 7 and No. 8), suggesting that Innexin may play an important role in U. unicinctus apical tufts, circumoral cilia and telotrochs genesis. This study revealed the characteristics of ciliogenesis on the body surface of U. unicinctus embryos and larvae, providing basic data for exploring the molecular mechanism of ciliogenesis on the body surface.

Keywords:  Innexin; Urechis unicinctus; ciliary type; ciliogenesis

DOI:  https://doi.org/10.3390/ijms241411537