Mammalian dentition exhibits distinct heterodonty, with more simple teeth located in the anterior area of the jaw and more complex teeth situated posteriorly. While some region-specific differences in signalling have been described previously, here we performed a comprehensive analysis of gene expression at the early stages of odontogenesis to obtain complete knowledge of the signalling pathways involved in early jaw patterning. Gene expression was analysed separately on anterior and posterior areas of the lower jaw at two early stages (E11.5 and E12.5) of odontogenesis. Gene expression profiling revealed distinct region-specific expression patterns in mouse mandibles, including several known BMP and FGF signalling members and we also identified several new molecules exhibiting significant differences in expression along the anterior-posterior axis, which potentially can play the role during incisor and molar specification. Next, we followed one of the anterior molecules, SATB2, which was expressed not only in the anterior mesenchyme where incisor germs are initiated, however, we uncovered a distinct SATB2-positive region in the mesenchyme closely surrounding molars. Satb2-deficient animals demonstrated defective incisor development confirming a crucial role of SATB2 in formation of anterior teeth. On the other hand, ectopic tooth germs were observed in the molar area indicating differential effect of Satb2-deficiency in individual jaw regions. In conclusion, our data provide a rich source of fundamental information, which can be used to determine molecular regulation driving early embryonic jaw patterning and serve for a deeper understanding of molecular signalling directed towards incisor and molar development.

• Klíčová slova
• Incisor, Lower jaw, Microarray, Molar, Mouse, Satb2,
• MeSH
• mandibula * metabolismus   embryologie   MeSH
• myši MeSH
• odontogeneze * genetika   MeSH
• řezáky metabolismus   embryologie   růst a vývoj   MeSH
• rozvržení tělního plánu genetika   MeSH
• signální transdukce MeSH
• stanovení celkové genové exprese * MeSH
• transkripční faktory * genetika   metabolismus   MeSH
• vazebné proteiny DNA v oblastech připojení k matrix * genetika   metabolismus   MeSH
• vývojová regulace genové exprese * MeSH
• zuby metabolismus   embryologie   růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• SATB2 protein, mouse MeSH Prohlížeč
• transkripční faktory * MeSH
• vazebné proteiny DNA v oblastech připojení k matrix * MeSH

The Hindbrain Choroid Plexus is a complex, cerebrospinal fluid-secreting tissue that projects into the 4th vertebrate brain ventricle. Despite its irreplaceability in the development and homeostasis of the entire central nervous system, the research of Hindbrain Choroid Plexus and other Choroid Plexuses has been neglected by neuroscientists for decades. One of the obstacles is the lack of tools that describe the complex shape of the Hindbrain Choroid Plexus in the context of brain ventricles. Here we introduce an effective tool, termed ChOP-CT, for the noninvasive, X-ray micro-computed tomography-based, three-dimensional visualization and subsequent quantitative spatial morphological analysis of developing mouse Hindbrain Choroid Plexus. ChOP-CT can reliably quantify Hindbrain Choroid Plexus volume, surface area, length, outgrowth angle, the proportion of the ventricular space occupied, asymmetries and general shape alterations in mouse embryos from embryonic day 13.5 onwards. We provide evidence that ChOP-CT is suitable for the unbiased evaluation and detection of the Hindbrain Choroid Plexus alterations within various mutant embryos. We believe, that thanks to its versatility, quantitative nature and the possibility of automation, ChOP-CT will facilitate the analysis of the Hindbrain Choroid Plexus in the mouse models. This will ultimately accelerate the screening of the candidate genes and mechanisms involved in the onset of various Hindbrain Choroid Plexus-related diseases.

• Klíčová slova
• 3D visualization, Hindbrain choroid plexus, Morphometrics, X-ray micro-computed tomography,
• MeSH
• mozek MeSH
• mozkové komory * MeSH
• myši MeSH
• plexus chorioideus * diagnostické zobrazování   MeSH
• rentgenová mikrotomografie MeSH
• rombencefalon diagnostické zobrazování   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Xenopus laevis, the African clawed frog, is a versatile vertebrate model organism in various biological disciplines, prominently in developmental biology to study body plan reorganization during metamorphosis. However, a notable gap exists in the availability of comprehensive datasets encompassing Xenopus' late developmental stages. FINDINGS: This study utilized micro-computed tomography (micro-CT), a noninvasive 3-dimensional (3D) imaging technique with micrometer-scale resolution, to explore the developmental dynamics and morphological changes in Xenopus laevis. Our approach involved generating high-resolution images and computed 3D models of developing Xenopus specimens, spanning from premetamorphosis tadpoles to fully mature adults. This dataset enhances our understanding of vertebrate development and supports various analyses. We conducted a careful examination, analyzing body size, shape, and morphological features, focusing on skeletogenesis, teeth, and organs like the brain and gut at different stages. Our analysis yielded valuable insights into 3D morphological changes during Xenopus' development, documenting details previously unrecorded. These datasets hold the solid potential for further morphological and morphometric analyses, including segmentation of hard and soft tissues. CONCLUSIONS: Our repository of micro-CT scans represents a significant resource that can enhance our understanding of Xenopus' development and the associated morphological changes in the future. The widespread utility of this amphibian species, coupled with the exceptional quality of our scans, which encompass a comprehensive series of developmental stages, opens up extensive opportunities for their broader research application. Moreover, these scans can be used in virtual reality, 3D printing, and educational contexts, further expanding their value and impact.

• Klíčová slova
• Xenopus laevis, development, micro–computed tomography, morphological changes, vertebrates,
• MeSH
• biologická proměna MeSH
• larva růst a vývoj   MeSH
• rentgenová mikrotomografie * metody   MeSH
• Xenopus laevis * růst a vývoj   MeSH
• zobrazování trojrozměrné * metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Primary cilia are cellular surface projections enriched in receptors and signaling molecules, acting as signaling hubs that respond to stimuli. Malfunctions in primary cilia have been linked to human diseases, including retinopathies and ocular defects. Here, we focus on TMEM107, a protein localized to the transition zone of primary cilia. TMEM107 mutations were found in patients with Joubert and Meckel-Gruber syndromes. A mouse model lacking Tmem107 exhibited eye defects such as anophthalmia and microphthalmia, affecting retina differentiation. Tmem107 expression during prenatal mouse development correlated with phenotype occurrence, with enhanced expression in differentiating retina and optic stalk. TMEM107 deficiency in retinal organoids resulted in the loss of primary cilia, down-regulation of retina-specific genes, and cyst formation. Knocking out TMEM107 in human ARPE-19 cells prevented primary cilia formation and impaired response to Smoothened agonist treatment because of ectopic activation of the SHH pathway. Our data suggest TMEM107 plays a crucial role in early vertebrate eye development and ciliogenesis in the differentiating retina.

• MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• myši MeSH
• polycystická choroba ledvin * genetika   MeSH
• poruchy ciliární motility * genetika   metabolismus   MeSH
• retina metabolismus   MeSH
• retinopathia pigmentosa * metabolismus   MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• membránové proteiny MeSH
• TMEM107 protein, human MeSH Prohlížeč
• Tmem107 protein, mouse MeSH Prohlížeč

Motor neuron (MN) development and nerve regeneration requires orchestrated action of a vast number of molecules. Here, we identify SorCS2 as a progranulin (PGRN) receptor that is required for MN diversification and axon outgrowth in zebrafish and mice. In zebrafish, SorCS2 knockdown also affects neuromuscular junction morphology and fish motility. In mice, SorCS2 and PGRN are co-expressed by newborn MNs from embryonic day 9.5 until adulthood. Using cell-fate tracing and nerve segmentation, we find that SorCS2 deficiency perturbs cell-fate decisions of brachial MNs accompanied by innervation deficits of posterior nerves. Additionally, adult SorCS2 knockout mice display slower motor nerve regeneration. Interestingly, primitive macrophages express high levels of PGRN, and their interaction with SorCS2-positive motor axon is required during axon pathfinding. We further show that SorCS2 binds PGRN to control its secretion, signaling, and conversion into granulins. We propose that PGRN-SorCS2 signaling controls MN development and regeneration in vertebrates.

• Klíčová slova
• CP: Developmental biology, CP: Neuroscience, SorCS2, VPS10p-D receptors, image segmentation, light-sheet microscopy, motor neurons, nerve injury, neurodevelopment, neurotrophic signaling, progranulin, zebrafish,
• MeSH
• dánio pruhované * metabolismus   MeSH
• granuliny MeSH
• mezibuněčné signální peptidy a proteiny * MeSH
• motorické neurony metabolismus   MeSH
• myši knockoutované MeSH
• myši MeSH
• progranuliny MeSH
• proteiny nervové tkáně metabolismus   MeSH
• receptory buněčného povrchu metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• granuliny MeSH
• mezibuněčné signální peptidy a proteiny * MeSH
• progranuliny MeSH
• proteiny nervové tkáně MeSH
• receptory buněčného povrchu MeSH
• SorCS2 protein, mouse MeSH Prohlížeč

Mineralized tissues, such as bones or teeth, are essential structures of all vertebrates. They enable rapid movement, protection, and food processing, in addition to providing physiological functions. Although the development, regeneration, and pathogenesis of teeth and bones have been intensely studied, there is currently no tool to accurately follow the dynamics of growth and healing of these vital tissues in space and time. Here, we present the BEE-ST (Bones and tEEth Spatio-Temporal growth monitoring) approach, which allows precise quantification of development, regeneration, remodeling, and healing in any type of calcified tissue across different species. Using mouse teeth as model the turnover rate of continuously growing incisors was quantified, and role of hard/soft diet on molar root growth was shown. Furthermore, the dynamics of bones and teeth growth in lizards, frogs, birds, and zebrafish was uncovered. This approach represents an effective, highly reproducible, and versatile tool that opens up diverse possibilities in developmental biology, bone and tooth healing, tissue engineering, and disease modeling.

• MeSH
• dánio pruhované * MeSH
• kosti a kostní tkáň MeSH
• myši MeSH
• vývoj kostí MeSH
• zubní kořen MeSH
• zuby * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• tisková chyba MeSH

In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.

• MeSH
• celogenomová asociační studie * MeSH
• energetický metabolismus * genetika   MeSH
• ferritin genetika   MeSH
• ledviny MeSH
• lidé MeSH
• neandertálci MeSH
• tělesná hmotnost MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ferritin MeSH

Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1Ndr/Ndr mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non-invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1Ndr/Ndr mice, using retina as a model. Jag1Ndr/Ndr mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex-specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non-invasive vascular analysis in patients. Finally, Jag1Ndr/Ndr mice represent a new model for vascular compromise in ALGS.

• Klíčová slova
• Alagille syndrome, Bleeding, Jagged1, Notch, Vasculature,
• MeSH
• Alagillův syndrom * komplikace   MeSH
• myši MeSH
• pohlavní dimorfismus MeSH
• retina MeSH
• rizikové faktory MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH

There are major differences in duration and scale at which limb development and regeneration proceed, raising the question to what extent regeneration is a recapitulation of development. We address this by analyzing skeletal elements using a combination of micro-CT imaging, molecular profiling and clonal cell tracing. We find that, in contrast to development, regenerative skeletal growth is accomplished based entirely on cartilage expansion prior to ossification, not limiting the transversal cartilage expansion and resulting in bulkier skeletal parts. The oriented extension of salamander cartilage and bone appear similar to the development of basicranial synchondroses in mammals, as we found no evidence for cartilage stem cell niches or growth plate-like structures during neither development nor regeneration. Both regenerative and developmental ossification in salamanders start from the cortical bone and proceeds inwards, showing the diversity of schemes for the synchrony of cortical and endochondral ossification among vertebrates.

• MeSH
• buněčné dělení MeSH
• chrupavka MeSH
• kosti a kostní tkáň MeSH
• osteogeneze * MeSH
• savci MeSH
• Urodela * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH