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Seminars in Cell & Developmental Biology 2024Hox genes are important regulators in animal development. They often show a mosaic of conserved (e.g., longitudinal axis patterning) and lineage-specific novel functions... (Review)
Review
Hox genes are important regulators in animal development. They often show a mosaic of conserved (e.g., longitudinal axis patterning) and lineage-specific novel functions (e.g., development of skeletal, sensory, or locomotory systems). Despite extensive research over the past decades, it remains controversial at which node in the animal tree of life the Hox cluster evolved. Its presence already in the last common metazoan ancestor has been proposed, although the genomes of both putative earliest extant metazoan offshoots, the ctenophores and the poriferans, are devoid of Hox sequences. The lack of Hox genes in the supposedly "simple"-built poriferans and their low number in cnidarians and the basally branching bilaterians, the xenacoelomorphs, seems to support the classical notion that the number of Hox genes is correlated with the degree of animal complexity. However, the 4-fold increase of the Hox cluster in xiphosurans, a basally branching chelicerate clade, as well as the situation in some teleost fishes that show a multitude of Hox genes compared to, e.g., human, demonstrates, that there is no per se direct correlation between organismal complexity and Hox number. Traditional approaches have tried to base homology on the morphological level on shared expression profiles of individual genes, but recent data have shown that, in particular with respect to Hox and other regulatory genes, complex gene-gene interactions rather than expression signatures of individual genes alone are responsible for shaping morphological traits during ontogeny. Accordingly, for sound homology assessments and reconstructions of character evolution on organ system level, additional independent datasets (e.g., morphological, developmental) need to be included in any such analyses. If supported by solid data, proposed structural homology should be regarded as valid and not be rejected solely on the grounds of non-parsimonious distribution of the character over a given phylogenetic topology.
Topics: Animals; Humans; Phylogeny; Homeodomain Proteins; Evolution, Molecular; Cnidaria; Genes, Homeobox; Multigene Family
PubMed: 36670036
DOI: 10.1016/j.semcdb.2023.01.007 -
Nature Communications Oct 2022Intracellular RNA localization is a widespread and dynamic phenomenon that compartmentalizes gene expression and contributes to the functional polarization of cells....
Intracellular RNA localization is a widespread and dynamic phenomenon that compartmentalizes gene expression and contributes to the functional polarization of cells. Thus far, mechanisms of RNA localization identified in Drosophila have been based on a few RNAs in different tissues, and a comprehensive mechanistic analysis of RNA localization in a single tissue is lacking. Here, by subcellular spatial transcriptomics we identify RNAs localized in the apical and basal domains of the columnar follicular epithelium (FE) and we analyze the mechanisms mediating their localization. Whereas the dynein/BicD/Egl machinery controls apical RNA localization, basally-targeted RNAs require kinesin-1 to overcome a default dynein-mediated transport. Moreover, a non-canonical, translation- and dynein-dependent mechanism mediates apical localization of a subgroup of dynein-activating adaptor-encoding RNAs (BicD, Bsg25D, hook). Altogether, our study identifies at least three mechanisms underlying RNA localization in the FE, and suggests a possible link between RNA localization and dynein/dynactin/adaptor complex formation in vivo.
Topics: Animals; Dyneins; Drosophila Proteins; Dynactin Complex; Kinesins; Transcriptome; RNA, Messenger; Drosophila; RNA; Microtubules
PubMed: 36289223
DOI: 10.1038/s41467-022-34004-2 -
Developmental Biology Jan 2022While the epithelial cell cortex displays profound asymmetries in protein distribution and morphology along the apico-basal axis, the extent to which the cytoplasm is...
While the epithelial cell cortex displays profound asymmetries in protein distribution and morphology along the apico-basal axis, the extent to which the cytoplasm is similarly polarized within epithelial cells remains relatively unexplored. We show that cytoplasmic organelles within C. elegans embryonic intestinal cells develop extensive apico-basal polarity at the time they establish cortical asymmetry. Nuclei and conventional endosomes, including early endosomes, late endosomes, and lysosomes, become polarized apically. Lysosome-related gut granules, yolk platelets, and lipid droplets become basally enriched. Removal of par-3 activity does not disrupt organelle positioning, indicating that cytoplasmic apico-basal asymmetry is independent of the PAR polarity pathway. Blocking the apical migration of nuclei leads to the apical positioning of gut granules and yolk platelets, whereas the asymmetric localization of conventional endosomes and lipid droplets is unaltered. This suggests that nuclear positioning organizes some, but not all, cytoplasmic asymmetries in this cell type. We show that gut granules become apically enriched when WHT-2 and WHT-7 function is disrupted, identifying a novel role for ABCG transporters in gut granule positioning during epithelial polarization. Analysis of WHT-2 and WHT-7 ATPase mutants is consistent with a WHT-2/WHT-7 heterodimer acting as a transporter in gut granule positioning. In wht-2(-) mutants, the polarized distribution of other organelles is not altered and gut granules do not take on characteristics of conventional endosomes that could have explained their apical mispositioning. During epithelial polarization wht-2(-) gut granules exhibit a loss of the Rab32/38 family member GLO-1 and ectopic expression of GLO-1 is sufficient to rescue the basal positioning of wht-2(-) and wht-7(-) gut granules. Furthermore, depletion of GLO-1 causes the mislocalization of the endolysosomal RAB-7 to gut granules and RAB-7 drives the apical mispositioning of gut granules when GLO-1, WHT-2, or WHT-7 function is disrupted. We suggest that ABC transporters residing on gut granules can regulate Rab dynamics to control organelle positioning during epithelial polarization.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Polarity; Epithelial Cells; Intestinal Mucosa; Organelles
PubMed: 34597675
DOI: 10.1016/j.ydbio.2021.09.007 -
Journal of Cell Science Mar 2021Hippo signaling mediates influences of cytoskeletal tension on organ growth. TRIP6 and LIMD1 have each been identified as being required for tension-dependent inhibition...
Hippo signaling mediates influences of cytoskeletal tension on organ growth. TRIP6 and LIMD1 have each been identified as being required for tension-dependent inhibition of the Hippo pathway LATS kinases and their recruitment to adherens junctions, but the relationship between TRIP6 and LIMD1 was unknown. Using siRNA-mediated gene knockdown, we show that TRIP6 is required for LIMD1 localization to adherens junctions, whereas LIMD1 is not required for TRIP6 localization. TRIP6, but not LIMD1, is also required for the recruitment of vinculin and VASP to adherens junctions. Knockdown of TRIP6 or vinculin, but not of LIMD1, also influences the localization of myosin and F-actin. In TRIP6 knockdown cells, actin stress fibers are lost apically but increased basally, and there is a corresponding increase in the recruitment of vinculin and VASP to basal focal adhesions. Our observations identify a role for TRIP6 in organizing F-actin and maintaining tension at adherens junctions that could account for its influence on LIMD1 and LATS. They also suggest that focal adhesions and adherens junctions compete for key proteins needed to maintain attachments to contractile F-actin.
Topics: Actin Cytoskeleton; Actins; Adherens Junctions; Cytoskeleton; Focal Adhesions; Vinculin
PubMed: 33558314
DOI: 10.1242/jcs.247866 -
The EMBO Journal Nov 2023The establishment and maintenance of apical-basal polarity is a fundamental step in brain development, instructing the organization of neural progenitor cells (NPCs) and...
The establishment and maintenance of apical-basal polarity is a fundamental step in brain development, instructing the organization of neural progenitor cells (NPCs) and the developing cerebral cortex. Particularly, basally located extracellular matrix (ECM) is crucial for this process. In vitro, epithelial polarization can be achieved via endogenous ECM production, or exogenous ECM supplementation. While neuroepithelial development is recapitulated in neural organoids, the effects of different ECM sources in tissue morphogenesis remain underexplored. Here, we show that exposure to a solubilized basement membrane matrix substrate, Matrigel, at early neuroepithelial stages causes rapid tissue polarization and rearrangement of neuroepithelial architecture. In cultures exposed to pure ECM components or unexposed to any exogenous ECM, polarity acquisition is slower and driven by endogenous ECM production. After the onset of neurogenesis, tissue architecture and neuronal differentiation are largely independent of the initial ECM source, but Matrigel exposure has long-lasting effects on tissue patterning. These results advance the knowledge on mechanisms of exogenously and endogenously guided morphogenesis, demonstrating the self-sustainability of neuroepithelial cultures by endogenous processes.
Topics: Humans; Extracellular Matrix; Morphogenesis; Organoids
PubMed: 37842725
DOI: 10.15252/embj.2022113213 -
PhytoKeys 2023(Ranunculaceae), a new species from Laojun Shan in Luanchuan county, Henan province, central China, is here illustrated and described. It is morphologically similar to...
(Ranunculaceae), a new species from Laojun Shan in Luanchuan county, Henan province, central China, is here illustrated and described. It is morphologically similar to in having 3-lobed and subreniform basal leaves, 3-lobed cauline leaves, and small flowers with reflexed and caducous sepals, but differs by having slender and basally slightly thickened roots (vs. fusiform), prostrate stems (vs. erect), obliquely ovoid and glabrous carpels and achenes (vs. widely ovoid and puberulous), longer styles in the carpels (ca. 1.2 mm vs. 0.6-0.8 mm) and achenes (ca. 1.8 mm vs. 0.6-0.8 mm), and glabrous receptacles (vs. sparsely puberulous). , currently known only from its type locality, is geographically isolated from , a species widely distributed in Gansu, Qinghai, Sichuan, Xizang (Tibet) and Yunnan, China. The distribution map of this new species and its putative closest ally, , is also provided.
PubMed: 37251614
DOI: 10.3897/phytokeys.220.96799 -
Cell Structure and Function Oct 2016Polarized epithelial cells contain a characteristic array of microtubules in which non-centrosomal microtubules are aligned along the apical-to-basal axis of the cell... (Review)
Review
Polarized epithelial cells contain a characteristic array of microtubules in which non-centrosomal microtubules are aligned along the apical-to-basal axis of the cell with their minus ends oriented towards the apical pole. Although this unique orientation of microtubules was discovered in the late 1980s, how this orientation is established remains unresolved partly because of limited information about molecular factors that regulate the minus ends of non-centrosomal microtubules. Recent studies, however, identified novel minus end-associated proteins, revealing mechanisms by which the polarized arrays of microtubules are established in epithelial cells. These studies have also demonstrated the importance of apico-basally orientated microtubules in intra-structural organization of cells. This review focuses on recent progress of our understanding of the molecular basis for epithelium-specific microtubule assembly and function.
Topics: Animals; Epithelium; Intercellular Junctions; Microtubule-Associated Proteins; Microtubules; Models, Molecular
PubMed: 27615606
DOI: 10.1247/csf.16015 -
Annals of the New York Academy of... Oct 2022Epithelial cells are polarized with defined apical tight junctions (TJs), lateral adherens junctions (AJs), and basal integrin-matrix interactions. However, it is...
Epithelial cells are polarized with defined apical tight junctions (TJs), lateral adherens junctions (AJs), and basal integrin-matrix interactions. However, it is increasingly recognized that resident cell junction proteins can be found in varying locations and with previously unrecognized functions. Our study here presents the nanoarchitecture and nanocolocalization of cell junction proteins in culture and tissue by stochastic optical reconstruction microscopy (STORM). The Z-axial view of noncancerous MDCK-II and PZ-HPV-7 cell-cell junctions resolved β-catenin and p120 localizations to TJs and AJs, with p120 apical to β-catenin and colocalizing with TJ protein claudin-7. More basally, p120 and β-catenin become colocalized. This topography was lost in isogenic Ras-transformed MDCK cells and cancerous PC3 cells, where p120 becomes basally localized in relation to β-catenin. Claudin-7 gene conditional knockout (cKO) in mice also have altered polarity of p120 relative to β-catenin, like that seen in normal-to-cancer cell phenotypic transformation. Additionally, claudin-7 cKO resulted in redistribution and relocalization of other cell junction proteins, including claudin-1, zonula occludens-1, integrin α2, epithelial cell adhesion molecule, and focal adhesion kinase (FAK); specifically, integrin α2 and FAK were observed at the apical-lateral compartment. Our data show that STORM reveals regional cellular junction nanoarchitecture previously uncharacterized, providing new insight into potential trans-compartmental modulation of protein functions.
Topics: Adherens Junctions; Animals; Cadherins; Claudin-1; Claudins; Epithelial Cell Adhesion Molecule; Epithelial Cells; Focal Adhesion Protein-Tyrosine Kinases; Integrin alpha2; Mice; Microscopy; Tight Junctions; beta Catenin
PubMed: 35819053
DOI: 10.1111/nyas.14855 -
Autophagy Apr 2023Macroautophagy/autophagy occurs basally under nutrient-rich conditions in most mammalian cells, contributing to protein and organelle quality control, and protection...
Macroautophagy/autophagy occurs basally under nutrient-rich conditions in most mammalian cells, contributing to protein and organelle quality control, and protection against aging and neurodegeneration. During autophagy, lysosomes are heavily utilized via their fusion with autophagosomes and must be repopulated to maintain autophagic degradative capacity. During starvation-induced autophagy, lysosomes are generated via biogenesis under the control of TFEB (transcription factor EB), or by the recycling of autolysosome membranes via autophagic lysosome reformation (ALR). However, these lysosome repopulation processes do not operate under nutrient-rich conditions. In our recent study, we identify a sequential phosphoinositide conversion pathway that enables lysosome repopulation under nutrient-rich conditions to facilitate basal autophagy. Phosphatidylinositol-3,4-bisphosphate (PtdIns[3,4]P) signals generated downstream of phosphoinositide 3-kinase alpha (PI3Kα) during growth factor stimulation are converted to phosphatidylinositol-3-phosphate (PtdIns3P) on endosomes by INPP4B (inositol polyphosphate-4-phosphatase type II B). We show that PtdIns3P is retained as endosomes mature into endolysosomes, and serves as a substrate for PIKFYVE (phosphoinositide kinase, FYVE-type zinc finger containing) to generate phosphatidylinositol-3,5-bisphosphate (PtdIns[3,5]P) to promote SNX2-dependent lysosome reformation, basal autophagic flux and protein aggregate degradation. Therefore, endosome maturation couples nutrient signaling to lysosome repopulation during basal autophagy by delivering PI3Kα-derived PtdIns3P to endolysosomes for PtdIns(3,5)P-dependent lysosome reformation. ALR: autophagic lysosome reformation; INPP4B: inositol polyphosphate-4-phosphatase type II B; PI3Kα: phosphoinositide 3-kinase alpha; PIKFYVE: phosphoinositide kinase FYVE-type zinc finger containing; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns(3,4)P: phosphatidylinositol-3,4-bisphosphate; PtdIns(3,5)P phosphatidylinositol-3,5-bisphosphate; SNX2 sorting nexin 2; PIK3C3/VPS34 phosphatidylinositol 3-kinase catalytic subunit type 3.
Topics: Animals; Phosphatidylinositols; Autophagy; Phosphatidylinositol 3-Kinases; 1-Phosphatidylinositol 4-Kinase; Phosphatidylinositol Phosphates; Lysosomes; Endosomes; Phosphoric Monoester Hydrolases; Nutrients; Phosphatidylinositol 3-Kinase; Polyphosphates; Inositol; Mammals
PubMed: 36103410
DOI: 10.1080/15548627.2022.2124499 -
The Prostate Sep 2018Rare prostate carcinomas aberrantly express p63 and have an immunophenotype intermediate between basal and luminal cells. Here, we performed gene expression profiling on...
BACKGROUND
Rare prostate carcinomas aberrantly express p63 and have an immunophenotype intermediate between basal and luminal cells. Here, we performed gene expression profiling on p63-expressing prostatic carcinomas and compared them to usual-type adenocarcinoma. We identify ETS2 as highly expressed in p63-expressing prostatic carcinomas and benign prostate basal cells, with lower expression in luminal cells and primary usual-type adenocarcinomas.
METHODS
A total of 8 p63-expressing prostate carcinomas at radical prostatectomy were compared to 358 usual-type adenocarcinomas by gene expression profiling performed on formalin fixed paraffin embedded tumor tissue using Affymetrix 1.0 ST microarrays. Correlation between differentially expressed genes and TP63 expression was performed in 5239 prostate adenocarcinomas available in the Decipher GRID. For validation, ETS2 in situ hybridization was performed on 19 p63-expressing prostate carcinomas and 30 usual-type adenocarcinomas arrayed on tissue microarrays (TMA).
RESULTS
By gene expression, p63-expressing prostate carcinomas showed low cell cycle activity and low Decipher prognostic scores, but were predicted to have high Gleason grade compared to usual-type adenocarcinomas by gene expression signatures and morphology. Among the genes over-expressed in p63-expressing carcinoma relative to usual-type adenocarcinoma were known p63-regulated genes, along with ETS2, an ETS family member previously implicated as a prostate cancer tumor suppressor gene. Across several cohorts of prostate samples, ETS2 gene expression was correlated with TP63 expression and was significantly higher in benign prostate compared to usual-type adenocarcinoma. By in situ hybridization, ETS2 gene expression was high in benign basal cells, and low to undetectable in benign luminal cells or usual-type adenocarcinoma. In contrast, ETS2 was highly expressed in 95% (18/19) of p63-expressing prostate carcinomas.
CONCLUSIONS
ETS2 is a predominantly basally-expressed gene in the prostate, with low expression in usual-type adenocarcinoma and high expression in p63-expressing carcinomas. Given this pattern, the significance of ETS2 loss by deletion or mutation in usual-type adenocarcinomas is uncertain.
Topics: Adenocarcinoma; Biomarkers, Tumor; Gene Expression; Gene Expression Profiling; Humans; Immunohistochemistry; In Situ Hybridization; Male; Prostate; Prostatectomy; Prostatic Neoplasms; Proto-Oncogene Protein c-ets-2; RNA; Tissue Array Analysis; Transcription Factors; Tumor Suppressor Proteins
PubMed: 29761525
DOI: 10.1002/pros.23646