Expression and function of clift in the development of somatic gonadal precursors within the Drosophila mesoderm

M. Boyle; N. Bonini; S. DiNardo

doi:10.1242/dev.124.5.971

Expression and function of clift in the development of somatic gonadal precursors within the Drosophila mesoderm

Development ◽

10.1242/dev.124.5.971 ◽

1997 ◽

Vol 124 (5) ◽

pp. 971-982 ◽

Cited By ~ 13

Author(s):

M. Boyle ◽

N. Bonini ◽

S. DiNardo

Keyword(s):

Germ Cells ◽

Ectopic Expression ◽

Cell Types ◽

General Mechanism ◽

Visceral Mesoderm ◽

Regulatory Cascade ◽

Early Expression ◽

Gene Regulatory ◽

And Function ◽

Lateral Mesoderm

The gonad forms from cells of two lineages: the germline and soma. The somatic gonadal cells generate the various cell types within the testis or ovary that support gametogenesis. These cells derive from embryonic mesoderm, but how they are specified is unknown. Here, we describe a novel regulator of Drosophila gonadogenesis, clift, mutations in which abolish gonad formation. clift is expressed within somatic gonadal precursors as these cells first form, demonstrating that 9–12 cells are selected as somatic gonadal precursors within each of three posterior parasegments at early stages in gonadogenesis. Despite this early expression, somatic gonadal precursors are specified in the absence of clift function. However, they fail to maintain their fate and, as a consequence, germ cells do not coalesce into a gonad. In addition, using clift as a marker, we show that the anteroposterior and dorsoventral position of the somatic gonadal precursor cells within a parasegment are established by the secreted growth factor Wg, coupled with a gene regulatory hierarchy within the mesoderm. While loss of wg abolishes gonadal precursors, ectopic expression expands the population such that most cells within lateral mesoderm adopt gonadal precursor fates. Initial dorsoventral positioning of somatic gonadal precursors relies on a regulatory cascade that establishes dorsal fates within the mesoderm and is subsequently refined through negative regulation by bagpipe, a gene that specifies nearby visceral mesoderm. Thus, these studies identify essential regulators of gonadal precursor specification and differentiation and reveal novel aspects of the general mechanism whereby distinct fates are allocated within the mesoderm.

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Epigenetic reprogramming of cell identity: lessons from development for regenerative medicine

Clinical Epigenetics ◽

10.1186/s13148-021-01131-4 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Amitava Basu ◽

Vijay K. Tiwari

Keyword(s):

Regenerative Medicine ◽

Cell Types ◽

Direct Conversion ◽

Cellular Reprogramming ◽

Specific Cell ◽

Cell Type ◽

Pathological Conditions ◽

Gene Regulatory ◽

Induced Pluripotent ◽

And Function

AbstractEpigenetic mechanisms are known to define cell-type identity and function. Hence, reprogramming of one cell type into another essentially requires a rewiring of the underlying epigenome. Cellular reprogramming can convert somatic cells to induced pluripotent stem cells (iPSCs) that can be directed to differentiate to specific cell types. Trans-differentiation or direct reprogramming, on the other hand, involves the direct conversion of one cell type into another. In this review, we highlight how gene regulatory mechanisms identified to be critical for developmental processes were successfully used for cellular reprogramming of various cell types. We also discuss how the therapeutic use of the reprogrammed cells is beginning to revolutionize the field of regenerative medicine particularly in the repair and regeneration of damaged tissue and organs arising from pathological conditions or accidents. Lastly, we highlight some key challenges hindering the application of cellular reprogramming for therapeutic purposes.

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zfh-1 is required for germ cell migration and gonadal mesoderm development in Drosophila

Development ◽

10.1242/dev.125.4.655 ◽

1998 ◽

Vol 125 (4) ◽

pp. 655-666 ◽

Cited By ~ 19

Author(s):

H.T. Broihier ◽

L.A. Moore ◽

M. Van Doren ◽

S. Newman ◽

R. Lehmann

Keyword(s):

Cell Migration ◽

Germ Cell ◽

Germ Cells ◽

Ectopic Expression ◽

Homeodomain Protein ◽

Mesoderm Development ◽

Visceral Mesoderm ◽

Temporal Course ◽

Germ Cell Migration

In Drosophila as well as many vertebrate systems, germ cells form extraembryonically and migrate into the embryo before navigating toward gonadal mesodermal cells. How the gonadal mesoderm attracts migratory germ cells is not understood in any system. We have taken a genetic approach to identify genes required for germ cell migration in Drosophila. Here we describe the role of zfh-1 in germ cell migration to the gonadal mesoderm. In zfh-1 mutant embryos, the initial association of germ cells and gonadal mesoderm is blocked. Loss of zfh-1 activity disrupts the development of two distinct mesodermal populations: the caudal visceral mesoderm and the gonadal mesoderm. We demonstrate that the caudal visceral mesoderm facilitates the migration of germ cells from the endoderm to the mesoderm. Zfh-1 is also expressed in the gonadal mesoderm throughout the development of this tissue. Ectopic expression of Zfh-1 is sufficient to induce additional gonadal mesodermal cells and to alter the temporal course of gene expression within these cells. Finally, through analysis of a tinman zfh-1 double mutant, we show that zfh-1 acts in conjunction with tinman, another homeodomain protein, in the specification of lateral mesodermal derivatives, including the gonadal mesoderm.

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MOCHI enables discovery of heterogeneous interactome modules in 3D nucleome

10.1101/542092 ◽

2019 ◽

Cited By ~ 1

Author(s):

Dechao Tian ◽

Ruochi Zhang ◽

Yang Zhang ◽

Xiaopeng Zhu ◽

Jian Ma

Keyword(s):

Network Motif ◽

Interaction Network ◽

Cell Types ◽

Chromatin Interaction ◽

3D Genome ◽

Motif Clustering ◽

Gene Regulatory ◽

And Function ◽

Different Cell Types ◽

Transcription Factor Proteins

The composition of the cell nucleus is highly heterogeneous, with different constituents forming complex interactomes. However, the global patterns of these interwoven heterogeneous interactomes remain poorly understood. Here we focus on two different interactomes, chromatin interaction network and gene regulatory network, as a proof-of-principle, to identify heterogeneous interactome modules (HIMs) in the nucleus. Each HIM represents a cluster of gene loci that are in spatial contact more frequently than expected and that are regulated by the same group of transcription factor proteins. We develop a new algorithm MOCHI to facilitate the discovery of HIMs based on network motif clustering in heterogeneous interactomes. By applying MOCHI to five different cell types, we found that HIMs have strong spatial preference within the nucleus and exhibit distinct functional properties. Through integrative analysis, this work demonstrates the utility of MOCHI to identify HIMs, which may provide new perspectives on 3D genome organization and function.

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Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1421535112 ◽

2015 ◽

Vol 112 (13) ◽

pp. E1559-E1568 ◽

Cited By ~ 50

Author(s):

Fuguo Wu ◽

Tadeusz J. Kaczynski ◽

Santhosh Sethuramanujam ◽

Renzhong Li ◽

Varsha Jain ◽

...

Keyword(s):

Transcription Factors ◽

Cell Fate ◽

Ganglion Cells ◽

Ectopic Expression ◽

Cell Types ◽

Retinal Cell ◽

Retinal Ganglion ◽

Pou Domain ◽

Gene Enhancer ◽

Gene Regulatory

As with other retinal cell types, retinal ganglion cells (RGCs) arise from multipotent retinal progenitor cells (RPCs), and their formation is regulated by a hierarchical gene-regulatory network (GRN). Within this GRN, three transcription factors—atonal homolog 7 (Atoh7), POU domain, class 4, transcription factor 2 (Pou4f2), and insulin gene enhancer protein 1 (Isl1)—occupy key node positions at two different stages of RGC development. Atoh7 is upstream and is required for RPCs to gain competence for an RGC fate, whereas Pou4f2 and Isl1 are downstream and regulate RGC differentiation. However, the genetic and molecular basis for the specification of the RGC fate, a key step in RGC development, remains unclear. Here we report that ectopic expression of Pou4f2 and Isl1 in the Atoh7-null retina using a binary knockin-transgenic system is sufficient for the specification of the RGC fate. The RGCs thus formed are largely normal in gene expression, survive to postnatal stages, and are physiologically functional. Our results indicate that Pou4f2 and Isl1 compose a minimally sufficient regulatory core for the RGC fate. We further conclude that during development a core group of limited transcription factors, including Pou4f2 and Isl1, function downstream of Atoh7 to determine the RGC fate and initiate RGC differentiation.

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Cellular Expression and Subcellular Localization of Wwox Protein During Testicular Development and Spermatogenesis in Rats

Journal of Histochemistry & Cytochemistry ◽

10.1369/0022155421991629 ◽

2021 ◽

Vol 69 (4) ◽

pp. 257-270

Author(s):

Md Abdullah Al Mahmud ◽

Maki Noguchi ◽

Ayaka Domon ◽

Yuki Tochigi ◽

Kentaro Katayama ◽

...

Keyword(s):

Subcellular Localization ◽

Germ Cells ◽

Cell Types ◽

Reproductive Organs ◽

Testicular Development ◽

Adult Type ◽

Cellular Expression ◽

Testicular Cells ◽

Putative Tumor Suppressor ◽

And Function

A well-known putative tumor suppressor WW domain–containing oxidoreductase (Wwox) is highly expressed in hormonally regulated tissues and is considered important for the normal development and function of reproductive organs. In this study, we investigated the cellular and subcellular localization of Wwox in normal testes during postnatal days 0–70 using Western blotting and immunohistochemistry. Wwox is expressed in testes at all ages. Immunohistochemistry showed that fetal-type and adult-type Leydig cells, immature and mature Sertoli cells, and germ cells (from gonocytes to step 17 spermatids) expressed Wwox except peritubular myoid cells, step 18–19 spermatids, and mature sperm. Wwox localized diffusely in the cytoplasm with focal intense signals in all testicular cells. These signals gradually condensed in germ cells with their differentiation and colocalized with giantin for cis-Golgi marker and partially with golgin-97 for trans-Golgi marker. Biochemically, Wwox was detected in isolated Golgi-enriched fractions. But Wwox was undetectable in the nucleus. This subcellular localization pattern of Wwox was also confirmed in single-cell suspension. These findings indicate that Wwox is functional in most cell types of testis and might locate into Golgi apparatus via interaction with Golgi proteins. These unique localizations might be related to the function of Wwox in testicular development and spermatogenesis:

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Endogenous retrovirus rewired the gene regulatory network shared between primordial germ cells and naïve pluripotent cells in hominoids

10.1101/2021.03.09.434541 ◽

2021 ◽

Author(s):

Jumpei Ito ◽

Yasunari Seita ◽

Shohei Kojima ◽

Nicholas F. Parrish ◽

Kotaro Sasaki ◽

...

Keyword(s):

Gene Regulatory Network ◽

Germ Cells ◽

Regulatory Network ◽

Primordial Germ Cells ◽

Cell Types ◽

Endogenous Retrovirus ◽

Mammalian Evolution ◽

Comparative Transcriptome ◽

Pluripotent Cells ◽

Gene Regulatory

AbstractAlthough the gene regulatory network controlling germ cell development is critical for gamete integrity, this network has been substantially diversified during mammalian evolution. Here, we show that several hundred loci of LTR5_Hs, a hominoid-specific endogenous retrovirus (ERV), function as enhancers in both human primordial germ cells (PGCs) and naïve pluripotent cells. PGCs and naïve pluripotent cells exhibit a similar transcriptome signature, and the enhancers derived from LTR5_Hs contribute to establishing such similarity. LTR5_Hs appears to be activated by transcription factors critical in both cell types (KLF4, TFAP2C, NANOG, and CBFA2T2). Comparative transcriptome analysis between humans and macaques suggested that the expression of many genes in PGCs and naïve pluripotent cells has been upregulated by LTR5_Hs insertions in the hominoid lineage. Together, this study suggests that LTR5_Hs insertions have rewired and finetuned the gene regulatory network shared between PGCs and naïve pluripotent cells during hominoid evolution.TeaserA hominoid-specific ERV has rewired the gene regulatory network shared between PGCs and naïve pluripotent cells.

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Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614605 ◽

1999 ◽

Vol 81 (06) ◽

pp. 951-956 ◽

Cited By ~ 59

Author(s):

J. Corral ◽

R. González-Conejero ◽

J. Rivera ◽

F. Ortuño ◽

P. Aparicio ◽

...

Keyword(s):

Venous Thrombosis ◽

Cell Types ◽

Receptor Expression ◽

Case Control Studies ◽

Platelet Surface ◽

Vitro Analysis ◽

And Function ◽

In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

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Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽

10.3390/mi12080884 ◽

2021 ◽

Vol 12 (8) ◽

pp. 884

Author(s):

Marta Cherubini ◽

Scott Erickson ◽

Kristina Haase

Keyword(s):

Drug Testing ◽

Cell Types ◽

In Vitro Models ◽

Placental Development ◽

Scientific Challenge ◽

Induced Pluripotent ◽

And Function ◽

And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

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Plasma membrane integrity in health and disease: significance and therapeutic potential

Cell Discovery ◽

10.1038/s41421-020-00233-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Catarina Dias ◽

Jesper Nylandsted

Keyword(s):

Plasma Membrane ◽

Therapeutic Potential ◽

Calcium Influx ◽

Membrane Integrity ◽

Cell Types ◽

Physical Parameters ◽

Membrane Repair ◽

Plasma Membrane Integrity ◽

Repair Mechanisms ◽

And Function

AbstractMaintenance of plasma membrane integrity is essential for normal cell viability and function. Thus, robust membrane repair mechanisms have evolved to counteract the eminent threat of a torn plasma membrane. Different repair mechanisms and the bio-physical parameters required for efficient repair are now emerging from different research groups. However, less is known about when these mechanisms come into play. This review focuses on the existence of membrane disruptions and repair mechanisms in both physiological and pathological conditions, and across multiple cell types, albeit to different degrees. Fundamentally, irrespective of the source of membrane disruption, aberrant calcium influx is the common stimulus that activates the membrane repair response. Inadequate repair responses can tip the balance between physiology and pathology, highlighting the significance of plasma membrane integrity. For example, an over-activated repair response can promote cancer invasion, while the inability to efficiently repair membrane can drive neurodegeneration and muscular dystrophies. The interdisciplinary view explored here emphasises the widespread potential of targeting plasma membrane repair mechanisms for therapeutic purposes.

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