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opencc-zeroDec 2017View details →

Data from: Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis

The earliest developmental origins of dysmorphologies are poorly understood in many congenital diseases. They often remain elusive because the first signs of genetic misregulation may initiate as subtle changes in gene expression, which are hard to detect and can be obscured later in development by secondary effects. Here, we develop a method to trace the origins of phenotypic abnormalities by accurately quantifying the 3D spatial distribution of gene expression domains in developing organs. By applying geometric morphometrics to 3D gene expression data obtained by Optical Projection Tomography, we determined that our approach is sensitive enough to find regulatory abnormalities that have never been detected previously. We identified subtle but significant differences in the gene expression of a downstream target of the Fgfr2 mutation that were associated with Apert syndrome, demonstrating that these mouse models can further our understanding of limb defects in the human condition. Our method can be applied to different organ systems and models to investigate the etiology of malformations.

opencc-zeroDec 2015View details →

Data from: Ret and Etv4 promote directed movements of progenitor cells during renal branching morphogenesis

Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM), combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret−/− or Etv4−/− sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret/Etv4 signaling promotes directed cell movements in the ureteric bud tips, and suggest a model in which these cell movements mediate branching morphogenesis.

opencc-zeroDec 2019View details →

Data from: Mid-Cretaceous amber inclusions reveal morphogenesis of extinct rachis-dominated feathers

We describe three-dimensionally preserved feathers in mid-Cretaceous Burmese amber that share macro-morphological similarities (e.g., proportionally wide rachis with a "medial stripe") with lithic, two-dimensionally preserved rachis-dominated feathers. These feathers in amber reveal a unique ventrally concave and dorsoventrally thin rachis, and a dorsal groove (sometimes pigmented) that we identify as the "medial stripe" visible in many rachis-dominated rectrices of Mesozoic birds. The distally pennaceous portion of these feathers shows differentiated proximal and distal barbules, the latter with hooklets forming interlocking barbs. Micro-CT scans and transverse sections demonstrate the absence of histodifferentiated cortex and medullary pith of the rachis and barb rami. The highly differentiated barbules combined with the lack of obvious histodifferentiation of the barb rami or rachis suggests that these feathers could have been formed without the full suite and developmental interplay of intermediate filament alpha keratins and corneous beta-proteins that is employed in the cornification process of modern feathers. This study thus highlights how the development of these feathers might have differed from that of their modern counterparts, namely in the morphogenesis of the ventral components of the rachis and barb rami. We suggest that the concave ventral surface of the rachis of these Cretaceous feathers is not homologous with the ventral groove of modern rachises. Our study of these Burmese feathers also confirms previous claims, based on two-dimensional fossils, that they correspond to an extinct morphotype and it cautions about the common practice of extrapolating developmental aspects (and mechanical attributes) of modern feathers to those of stem birds (and their dinosaurian outgroups) because the latter need not to have developed through identical pathways.

opencc-zeroDec 2023View details →

Integrative single-cell multi-modal analyses reveal detailed spatial cellular organization directing human heart morphogenesis

<div> The heart, which is the first organ to develop, is highly dependent on its form to function. However, how diverse cardiac cell types spatially coordinate to create complex morphological structures critical for heart function remains to be elucidated. Here, we show that integration of single cell RNA-sequencing with high-resolution multiplexed error-robust fluorescent in situ hybridization (MERFISH) not only resolves the identity of cardiac cell types developing the human heart but also provides a spatial mapping of individual cells that enables illumination of their organization into cellular communities forming distinct cardiac structures. We discovered that many of these cardiac cell types further specified into subpopulations exclusive to specific communities, supporting their specialization according to cellular ecosystem and anatomic region. In particular, ventricular cardiomyocyte subpopulations displayed an unexpected complex laminar organization across the ventricular wall and formed, with other cell subpopulations, several cellular communities. Interrogating cell-cell interactions within these communities revealed signaling pathways orchestrating the spatial organization of cardiac cell subpopulations during ventricular wall morphogenesis. In vivo conditional genetic mouse models and in vitro human pluripotent stem cell studies confirmed an intricate multicellular PLXN-SEMA crosstalk among specific ventricular cardiomyocyte, fibroblast and endothelial cell subpopulations that directs the compaction of the ventricular wall layers. Thus, these detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodeling the human heart offer new insights into structural heart diseases as well as engineering complex multi-cellular tissues for human heart repair. </div>

opencc-zeroNov 2021View details →

Cooperation of membrane-translocated syntaxin4 and basement membrane for dynamic mammary epithelial morphogenesis

Mammary epithelia undergo dramatic morphogenesis after puberty. During pregnancy, luminal epithelial cells in ductal trees are arranged to form well-polarized cystic structures surrounded by a myoepithelial cell layer, an active supplier of the basement membrane (BM). Here, we identified a novel regulatory mechanism involved in this process by using a reconstituted BM-based three-dimensional culture and aggregates of a model mouse cell line, EpH4, that had either been manipulated for inducible expression of the t-SNARE protein syntaxin4 in an intact or signal peptide-connected form, or that were genetically deficient in syntaxin4. We found that cells extruded syntaxin4 upon stimulation with the lactogenic hormone, prolactin, which in turn accelerated the turnover of E-cadherin. In response to extracellular expression of syntaxin4, cell populations that were less affected by the BM actively migrated and integrated into the cell layer facing the BM. Concurrently, the BM-facing cells, which were simultaneously stimulated with syntaxin4 and BM, acquired unique epithelial characteristics to undergo dramatic cellular arrangement for cyst formation. These results highlight the importance of the concerted action of extracellular syntaxin4 extruded in response to the lactogenic hormone and BM components in epithelial morphogenesis.

opencc-by-4.0Oct 2021View details →

Integer topological defects organize stresses driving tissue morphogenesis

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opencc-by-4.0Dec 2018View details →

Fig. 1 in Integrative Studies on the Morphology, Morphogenesis and Molecular Phylogeny of a Soil Ciliate, Parakahliella macrostoma (Foissner, 1982) Berger et al., 1985 (Ciliophora, Hypotrichia)

Fig. 1. Sample sites and surrounding areas. (A) Map showing the locations of Maqu and Gulang, Gansu Province. (B) Location where Parakahliella macrostoma pop.1 was collected and surrounding areas. (C–E) Location where Parakahliella macrostoma pop.2 was collected and surrounding areas.

Fig. 9 in A mosaic of conserved and novel modes of gene expression and morphogenesis in mesoderm and muscle formation of a larval bivalve

Fig. 9 Comparative expression of Mox in Metazoa. X: absence of a Mox ortholog in the genome,?: no data available. Phylogeny after Laumer et al. (2019). Comparative analysis suggests that Mox has an

Fig. 1 in A mosaic of conserved and novel modes of gene expression and morphogenesis in mesoderm and muscle formation of a larval bivalve

Fig. 1 Expression of Brachyury (Dro-Bra) in Dreissena rostriformis gastrula and trochophore stages. Anterior is up. Black arrowheads indicate the blastopore/stomodaeum, sf marks the shell field, dotted line marks the region of the prototroch (pt). Scale bar equals 20 µm. a Lateral view of Dro-Bra in the ventral mesoderm. b Ventral view of mesodermal Dro-Bra expression. c Dro-Bra is expressed in the ventro-posterior mesoderm and in the developing foregut. d Mesodermal and endodermal expression of Dro-Bra, ventral view. The left and right lobes belong to the prototroch (pt). A, anterior; D, dorsal; P, posterior; V, ventral

Fig. 8 in A mosaic of conserved and novel modes of gene expression and morphogenesis in mesoderm and muscle formation of a larval bivalve

Fig. 8 Comparative expression of even-skipped (eve) in Metazoa. X: absence of an eve ortholog in the genome,?: no data available. Phylogeny after Laumer et al. (2019). The data currently available indicate that eve was expressed during ectoderm development in the

Fig. 7 in A mosaic of conserved and novel modes of gene expression and morphogenesis in mesoderm and muscle formation of a larval bivalve

Fig. 7 Comparative expression of Brachyury (Bra) in Metazoa. X: absence of a Brachyury ortholog in the genome,?: no data available, #: Bra expression in oocytes, in the choanocytes, and in the choanoderm, *: expression of Bra near the edge of potential 'outgrowth zones' (Martinelli & Spring, 2003). Phylogeny after Laumer et al.

Fig. 2 in A mosaic of conserved and novel modes of gene expression and morphogenesis in mesoderm and muscle formation of a larval bivalve

Fig. 2 Expression of evenskipped (Dro-eve) during early development in Dreissena rostriformis. Anterior is up. Black arrowheads indicate the blastopore/stomodaeum, dotted line marks the region of the prototroch (pt), and sf marks the shell field. Scale bar equals 20 µm. a Dro-eve is first expressed in the ventral mesoderm and in ectodermal cells of the shell field. b Dro-eve expression in the ventral mesoderm ventro-posteriorly of the shell field. c Ectodermal expression of Dro-eve in the shell field. d Dro-eve expression in the ventro-posterior mesoderm and in the shell field of the trochophore larva. e Mesodermal expression of Dro-eve in ventral view. A, anterior; D, dorsal; P, posterior; V, ventral

opencc-by-4.0Dec 2012View details →

Fig. 1 in Effects of Roscovitine on Schedule of Divisional Morphogenesis, Basal Bodies Proliferation and Cell Divisions in Tetrahymena thermophila

Fig. 1. Divisional morphogenesis and cytokinesis in untreated (control) T. thermophila. Cells were immunostained with the anti-centrin 20H5 antibody. A–F' stomatogenesis, stages I–VI; G–H cytokinesis. AF – an anarchic field, ARF – parental apical ring of filaments, mARF material for new ARF localised on in the proximal ends (couplets of BBs) of cortical rows in opisthe cell, FZ – fission zone, OA1 and OA2 – parental and new oral apparatuses, OC – parental oral crescent, nOC – new oral crescents in both daughter cells. Bar: 10 µm for A–H.

opencc-by-4.0Dec 2012View details →

Fig. 11 in Effects of Roscovitine on Schedule of Divisional Morphogenesis, Basal Bodies Proliferation and Cell Divisions in Tetrahymena thermophila

Fig. 11. Cortical structures of T. thermophila immunogoldlabelled with anti-cdc14A antibody. A – longitudinal section of the ciliated basal body; B – transversal section of the fragment of the cortical row; C – section at the level of basal bodies of oral membranelle. Kt – kinetodesmal fiber, pc – postciliary microtubules, arrowhead – filamentous material. Bar: 1 μm.

opencc-by-4.0Dec 2012View details →

Fig. 3 in Effects of Roscovitine on Schedule of Divisional Morphogenesis, Basal Bodies Proliferation and Cell Divisions in Tetrahymena thermophila

Fig. 3. Divisional morphogenesis and cytokinesis in T. thermophila after 5.5 h treatment with roscovitine. Cells were immunostained with the anti-centrin 20H5 antibody. A–C – stage VI of divisional morphogenesis; D–F' – cytokinesis; A and A' – ventral and dorsal views of the same cell. Other explanations as in Fig. 1. Bar in F': 10 µm for A–F'.

ClinicalTrials.gov28/100

Abutment Hydrophilicity on Soft Tissue Morphogenesis

ClinicalTrials.gov study NCT07082088. IPD Sharing: UNDECIDED. Countries: 0. Publications: 1.

restrictedIPD-UNDECIDEDFeb 2026View details →

publicNov 2021View details →

Cooperation of membrane-translocated syntaxin4 and basement membrane for dynamic mammary epithelial morphogenesis

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