scholarly journals Inducing your neighbors to become like you: Cell recruitment and its contribution to developmental patterning and growth

2020 ◽  
Vol 52 ◽  
Author(s):  
Luis Manuel Muñoz-Nava ◽  
Marycruz Flores-Flores ◽  
Marcos Nahmad
Keyword(s):  
Specific Cell ◽  
Cell Type ◽  
Recruitment Process ◽  
Cell Recruitment ◽  
Drosophila Wing ◽  
Differentiated Cells ◽  
Open Questions ◽  
Developmental Patterning ◽  
Type Population

Cell differentiation, proliferation, and morphogenesis are generally driven by instructive signals that are sent and interpreted by adjacent tissues, a process known as induction. Cell recruitment is a particular case of induction in which differentiated cells produce a signal that drives adjacent cells to differentiate into the same type as the inducers. Once recruited, these new cells may become inducers to continue the recruitment process, closing a feed-forward loop that propagates the growth of a specific cell-type population. So far, little attention has been given to cell recruitment as a developmental mechanism. Here, we review the components of cell recruitment and discuss its contribution to development in three different examples: the Drosophila wing, the vertebrate inner ear, and the mammalian thyroid gland. Finally, we posit some open questions about the role of cell recruitment in organ patterning and growth.

scholarly journals Role of GPER-Mediated Signaling in Testicular Functions and Tumorigenesis

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2115
Author(s):  
Adele Chimento ◽  
Arianna De Luca ◽  
Marta Claudia Nocito ◽  
Paola Avena ◽  
Davide La Padula ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Somatic Cells ◽  
Estrogen Signaling ◽  
Specific Cell ◽  
Cell Type ◽  
Cancer Cell Growth ◽  
Testicular Cells ◽  
G Protein Coupled ◽  
Receptor Family

Estrogen signaling plays important roles in testicular functions and tumorigenesis. Fifteen years ago, it was discovered that a member of the G protein-coupled receptor family, GPR30, which binds also with high affinity to estradiol and is responsible, in part, for the rapid non-genomic actions of estrogens. GPR30, renamed as GPER, was detected in several tissues including germ cells (spermatogonia, spermatocytes, spermatids) and somatic cells (Sertoli and Leydig cells). In our previous review published in 2014, we summarized studies that evidenced a role of GPER signaling in mediating estrogen action during spermatogenesis and testis development. In addition, we evidenced that GPER seems to be involved in modulating estrogen-dependent testicular cancer cell growth; however, the effects on cell survival and proliferation depend on specific cell type. In this review, we update the knowledge obtained in the last years on GPER roles in regulating physiological functions of testicular cells and its involvement in neoplastic transformation of both germ and somatic cells. In particular, we will focus our attention on crosstalk among GPER signaling, classical estrogen receptors and other nuclear receptors involved in testis physiology regulation.

scholarly journals Postnatal Lethality in Mice Lacking the Sax2 Homeobox Gene Homologous to Drosophila S59/slouch: Evidence for Positive and Negative Autoregulation

2003 ◽  
Vol 23 (24) ◽  
pp. 9046-9060 ◽  
Author(s):  
Ruth Simon ◽  
Thomas Lufkin
Keyword(s):  
Null Allele ◽  
Homeobox Gene ◽  
Premature Death ◽  
Specific Cell ◽  
Cell Type ◽  
High Similarity ◽  
Cell Specification ◽  
Ventral Neural Tube ◽  
Positive And Negative Feedback

ABSTRACT Homeobox gene transcription factors direct multiple functions during development. They are involved in early patterning of the embryo as well as cell specification, cell differentiation, and organogenesis. Here we describe a previously uncharacterized murine homeobox gene, Sax2, that shows high similarity to the Drosophila S59/slouch and murine Sax1 genes. We show that Sax2 gene expression occurs early during embryogenesis in the midbrain, the midbrain-hindbrain boundary, the ventral neural tube, the developing eye, and the apical ectodermal ridge of the limb. To determine the role of Sax2 during development, we generated a knockout mouse line by replacing part of the Sax2 coding sequences with the lacZ gene. The Sax2 null allele mutants exhibit a strong phenotype indicated by growth retardation starting immediately after birth and leading to premature death within the first 3 weeks postnatal. Intriguingly, our studies also demonstrated a striking autoregulation of the Sax2 gene in both positive- and negative-feedback mechanisms depending on the specific cell type expressing Sax2.

scholarly journals Hypoxia in Breast Cancer—Scientific Translation to Therapeutic and Diagnostic Clinical Applications

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Zhang ◽  
Hongyi Zhang ◽  
Minghong Wang ◽  
Thomas Schmid ◽  
Zhaochen Xin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Resistance ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Cell Recruitment ◽  
Tissue Invasion ◽  
Open Questions ◽  
Increased Risk ◽  
Genes Encoding

Breast cancer has been the leading cause of female cancer deaths for decades. Intratumoral hypoxia, mainly caused by structural and functional abnormalities in microvasculature, is often associated with a more aggressive phenotype, increased risk of metastasis and resistance to anti-malignancy treatments. The response of cancer cells to hypoxia is ascribed to hypoxia-inducible factors (HIFs) that activate the transcription of a large battery of genes encoding proteins promoting primary tumor vascularization and growth, stromal cell recruitment, extracellular matrix remodeling, cell motility, local tissue invasion, metastasis, and maintenance of the cancer stem cell properties. In this review, we summarized the role of hypoxia specifically in breast cancer, discuss the prognostic and predictive value of hypoxia factors, potential links of hypoxia and endocrine resistance, cancer hypoxia measurements, further involved mechanisms, clinical application of hypoxia-related treatments and open questions.

Role of angiogenesis factors in formation of metastatic niches.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15534-e15534
Author(s):  
Elena M. Frantsiyants ◽  
Oleg I. Kit ◽  
Irina V. Kaplieva ◽  
Yuriy A. Gevorkyan ◽  
Natalya V. Soldatkina ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factors ◽  
Tumor Cells ◽  
Comparison Group ◽  
Metastatic Tumor ◽  
Specific Cell ◽  
Cell Type ◽  
Metastatic Niche ◽  
Mesenchymal Transition

e15534 Background: A metastatic niche indicates a particular location with a specific cell type, epidermal-mesenchymal transition proteins and diffuse signals that are necessary for the growth of metastases. The purpose of the study was to determine levels of VEGFs, their receptors and TGFβ1 in tissues of gastric cancer (GC) and its metastatic niches: the peritoneum and omentum. Methods: The main group included 21 patients with metastatic GC T3-4аN0-3M1; comparison group – 17 non-cancer patients. Levels of VEGFA, VEGFC, sVEGFR1, sVEGFR3 and TGFβ1 in tissues were determined by standard ELISA methods. Results: Levels of growth factors in GC tissues were higher than in controls: VEGFA in T3-4аN0-3M1 – by 2.7 times, in T3-4аN0-3M0 – by 2.5 times; TGFβ1 in T3-4аN0-3M1 – by 5.6 times, in T3-4аN0-3M0 – by 3.5 times. VEGFA levels in primary gastric tumors were similar in all patients, while TGFβ1 in T3-4аN0-3M1 was 1.6 times (p < 0.05) higher than in T3-4аN0-3M0. VEGFA levels in T3-4аN0-3M1 exceeded control values: in the omentum – by 2.8, in the peritoneum – by 4.2 times. TGFβ1 in the omentum and peritoneum in T3-4аN0-3M1 was increased by 2.5 and 3.1 times respectively, compared to controls. Statistically significant differences in VEGFA and TGFβ1 levels in the omentum and peritoneum in T3-4аN0-3M0 were not found. Conclusions: GC is characterized by equally elevated levels of VEGFA, regardless of the presence or absence of metastases. In the omentum and peritoneum with metastases, high VEGF levels can be considered as one of the primary factors for the formation of signaling pathways between metastatic tumor cells and local non-tumor cells in premetastatic niches. Levels of TGFβ1 in the omentum and peritoneum increase only in patients with metastases, and in GC tissue they are increased to a greater extent than in patients without metastases. Probably, in case of T3-4aN0-3M0, the factor produced by the primary tumor was insufficient for its paracrine induction in the metastatic niche, and scattered cells could not transit from “sleeping” to the active state.

scholarly journals The Role of the Medial Septum—Associated Networks in Controlling Locomotion and Motivation to Move

2021 ◽  
Vol 15 ◽  
Author(s):  
Petra Mocellin ◽  
Sanja Mikulovic
Keyword(s):  
Theta Rhythm ◽  
Medial Septum ◽  
Brain Regions ◽  
Cell Populations ◽  
Specific Cell ◽  
Diagonal Band ◽  
Open Questions ◽  
Motivational Aspect ◽  
Novel Theory

The Medial Septum and diagonal Band of Broca (MSDB) was initially studied for its role in locomotion. However, the last several decades were focussed on its intriguing function in theta rhythm generation. Early studies relied on electrical stimulation, lesions and pharmacological manipulation, and reported an inconclusive picture regarding the role of the MSDB circuits. Recent studies using more specific methodologies have started to elucidate the differential role of the MSDB’s specific cell populations in controlling both theta rhythm and behaviour. In particular, a novel theory is emerging showing that different MSDB’s cell populations project to different brain regions and control distinct aspects of behaviour. While the majority of these behaviours involve movement, increasing evidence suggests that MSDB-related networks govern the motivational aspect of actions, rather than locomotion per se. Here, we review the literature that links MSDB, theta activity, and locomotion and propose open questions, future directions, and methods that could be employed to elucidate the diverse roles of the MSDB-associated networks.

scholarly journals Cell-type specialization in the brain is encoded by specific long-range chromatin topologies

2020 ◽  
Author(s):  
Warren Winick-Ng ◽  
Alexander Kukalev ◽  
Izabela Harabula ◽  
Luna Zea Redondo ◽  
Mandy Meijer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genome Architecture ◽  
Specific Cell ◽  
Genome Organisation ◽  
Cell Type ◽  
Topological Domains ◽  
3D Genome ◽  
Differentiated Cells ◽  
Cell Type Specific ◽  
The Brain

AbstractNeurons and oligodendrocytes are terminally differentiated cells that perform highly specialized functions, which depend on cascades of gene activation and repression to retain homeostatic control over a lifespan. Gene expression is regulated by three-dimensional (3D) genome organisation, from local levels of chromatin compaction to the organisation of topological domains and chromosome compartments. Whereas our understanding of 3D genome architecture has vastly increased in the past decade, it remains difficult to study specialized cells in their native environment without disturbing their activity. To develop the application of Genome Architecture Mapping (GAM) in small numbers of specialized cells in complex tissues, we combined GAM with immunoselection. We applied immunoGAM to map the genome architecture of specific cell populations in the juvenile/adult mouse brain: dopaminergic neurons (DNs) from the midbrain, pyramidal glutamatergic neurons (PGNs) from the hippocampus, and oligodendrocyte lineage cells (OLGs) from the cortex. We integrate 3D genome organisation with single-cell transcriptomics data, and find specific chromatin structures that relate with cell-type specific patterns of gene expression. We discover abundant changes in compartment organisation, especially a strengthening of heterochromatin compartments which establish strong contacts spanning tens of megabases, especially in brain cells. These compartments contain olfactory and taste receptor genes, which are de-repressed in a subpopulation of PGNs with molecular signatures of long-term potentiation (LTP). We also show extensive reorganisation of topological domains where activation of neuronal or oligodendrocyte genes coincides with formation of new TAD borders. Finally, we discover loss of TAD organisation, or ‘TAD melting’, at long (>1Mb) neuronal genes when they are most highly expressed. Our work shows that the 3D organisation of the genome is highly cell-type specific in terminally differentiated cells of the brain, and essential to better understand brain-specific mechanisms of gene regulation.

scholarly journals A dynamic cell recruitment process drives growth of the Drosophila wing by overscaling the Vestigial expression pattern

2019 ◽  
Author(s):  
Luis Manuel Muñoz-Nava ◽  
Hugo Ariel Alvarez ◽  
Marycruz Flores-Flores ◽  
Osvaldo Chara ◽  
Marcos Nahmad
Keyword(s):  
Imaginal Disc ◽  
Direct Evidence ◽  
Recruitment Process ◽  
Fluorescent Reporter ◽  
Cell Recruitment ◽  
Cell Divisions ◽  
Drosophila Wing ◽  
Undifferentiated Cells ◽  
Dynamic Cell ◽  
Cell Growth And Proliferation

AbstractOrgans mainly attain their size by cell growth and proliferation, but sometimes also grow through recruitment of undifferentiated cells. Here we investigate the participation of cell recruitment in establishing the pattern of Vestigial (Vg), the product of the wing selector gene in Drosophila. We find that the Vg pattern overscales along the dorsal-ventral (DV) axis of the wing imaginal disc, i.e., it expands faster than the DV length of the pouch. The overscaling of the Vg pattern cannot be explained by differential proliferation, apoptosis, or oriented-cell divisions, but can be recapitulated by a mathematical model that explicitly considers cell recruitment. By impairing cell recruitment genetically, we find that the Vg pattern almost perfectly scales and adult wings are approximately 20% smaller. Furthermore, using fluorescent reporter tools, we provide direct evidence that cell recruitment takes place in a specific time between early and mid third-instar larval development. Altogether, our work quantitatively shows when, how, and by how much cell recruitment shapes the Vg pattern and drives growth of the Drosophila wing.

scholarly journals Reorganisation of chromatin during erythroid differentiation

2019 ◽  
Vol 23 (1) ◽  
pp. 95-99
Author(s):  
A. A. Khabarova ◽  
A. S. Ryzhkova ◽  
N. R. Battulin
Keyword(s):  
Chromatin Structure ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Erythroid Differentiation ◽  
Gene Activity ◽  
Nuclear Space ◽  
Specific Cell ◽  
Cell Type ◽  
Differentiation Potential

A totipotent zygote has unlimited potential for differentiation into all cell types found in an adult organism. During ontogenesis proliferating and maturing cells gradually lose their differentiation potential, limiting the spectrum of possible developmental transitions to a specific cell type. Following the initiation of the developmental program cells acquire specific morphological and functional properties. Deciphering the mechanisms that coordinate shifts in gene expression revealed a critical role of three-dimensional chromatin structure in the regulation of gene activity during lineage commitment. Several levels of DNA packaging have been recently identified using chromosome conformation capture based techniques such a Hi-C. It is now clear that chromatin regions with high transcriptional activity assemble into Mb-scale compartments in the nuclear space, distinct from transcriptionally silent regions. More locally chromatin is organized into topological domains, serving as functionally insulated units with cell type – specific regulatory loop interactions. However, molecular mechanisms establishing and maintaining such 3D organization are yet to be investigated. Recent focus on studying chromatin reorganization accompanying cell cycle progression and cellular differentiation partially explained some aspects of 3D genome folding. Throughout erythropoiesis cells undergo a dramatic reorganization of the chromatin landscape leading to global nuclear condensation and transcriptional silencing, followed by nuclear extrusion at the final stage of mammalian erythropoiesis. Drastic changes of genome architecture and function accompanying erythroid differentiation seem to be an informative model for studying the ways of how genome organization and dynamic gene activity are connected. Here we summarize current views on the role of global rearrangement of 3D chromatin structure in erythroid differentiation.

scholarly journals A dynamic cell recruitment process drives growth of the Drosophila wing by overscaling the vestigial expression pattern

2020 ◽  
Vol 462 (2) ◽  
pp. 141-151
Author(s):  
Luis Manuel Muñoz-Nava ◽  
Hugo Ariel Alvarez ◽  
Marycruz Flores-Flores ◽  
Osvaldo Chara ◽  
Marcos Nahmad
Keyword(s):  
Expression Pattern ◽  
Recruitment Process ◽  
Cell Recruitment ◽  
Drosophila Wing ◽  
Dynamic Cell

Role of N- and O-glycans in polarized biosynthetic sorting

2006 ◽  
Vol 290 (1) ◽  
pp. C1-C10 ◽  
Author(s):  
Beth A. Potter ◽  
Rebecca P. Hughey ◽  
Ora A. Weisz
Keyword(s):  
Developmental Stage ◽  
Posttranslational Modifications ◽  
Biosynthetic Pathway ◽  
Cell Type ◽  
The Past ◽  
Differentiated Cells ◽  
Sorting Signals ◽  
Targeting Signals ◽  
Apical Sorting

The maintenance of proper epithelial function requires efficient sorting of newly synthesized and recycling proteins to the apical and basolateral surfaces of differentiated cells. Whereas basolateral protein sorting signals are generally confined to their cytoplasmic regions, apical targeting signals have been identified that localize to luminal, transmembrane, and cytoplasmic aspects of proteins. In the past few years, both N- and O-linked glycans have been identified as apical sorting determinants. Glycan structures are extraordinarily diverse and have tremendous information potential. Moreover, because the oligosaccharides added to a given protein can change depending on cell type and developmental stage, the potential exists for altering sorting pathways by modulation of the expression pattern of enzymes involved in glycan synthesis. In this review, we discuss the evidence for glycan-mediated apical sorting along the biosynthetic pathway and present possible mechanisms by which these common and heterogeneous posttranslational modifications might function as specific sorting signals.

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