Editorial

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Open AccessEditorial

by Robert W. Dettman

J. Dev. Biol. 2015, 3(3), 90-92; https://doi.org/10.3390/jdb3030090 - 23 Sep 2015

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While non-blood cell lineage has been studied for decades by developmental biologists, only recently has it been considered in disease. This is partly due to a lack of suitable reagents in experimental models, but it is also the result of a failure to [...] Read more.

While non-blood cell lineage has been studied for decades by developmental biologists, only recently has it been considered in disease. This is partly due to a lack of suitable reagents in experimental models, but it is also the result of a failure to understand the ability of cells to move or differentiate in pathological environments. This Editorial gives a quick overview of the Special Issue “Cell Fate Decisions in Development and Disease” and underscores the importance of understanding the mechanisms of cell fate determination and lineage. Full article

(This article belongs to the Special Issue Cell Fate Decisions in Development and Disease)

Research

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Open AccessArticle

Restricted Pax3 Deletion within the Neural Tube Results in Congenital Hydrocephalus

by Hong-Ming Zhou and Simon J. Conway

J. Dev. Biol. 2016, 4(1), 7; https://doi.org/10.3390/jdb4010007 - 01 Feb 2016

Cited by 4 | Viewed by 7252

Abstract

Congenital hydrocephalus is a common birth-defect whose developmental origins are poorly understood. Pax3-null mutants show defects in myogenesis, neural tube closure, neural crest morphogenesis, and heart development that, consequently, results in embryonic lethality. Here we demonstrate that conditional deletion of the mouse [...] Read more.

Congenital hydrocephalus is a common birth-defect whose developmental origins are poorly understood. Pax3-null mutants show defects in myogenesis, neural tube closure, neural crest morphogenesis, and heart development that, consequently, results in embryonic lethality. Here we demonstrate that conditional deletion of the mouse Pax3 transcription factor results in fully-penetrant congenital obstructive hydrocephalus. To identify the role of Pax3 during cranial development, we deleted Pax3 within the neuroepithelium (via Pax7^−Cre), in the neural crest (via P0-Cre), and in both the neuroepithelium and the neural crest (via Wnt1-Cre). Only conditional mutants generated using Pax7^−Cre or Wnt1-Cre developed early onset congenital hydrocephalus due to stenosis of the third ventricle, suggesting that loss of neuroepithelial Pax3 is sufficient to disturb third ventricle morphogenesis. Dilation of lateral ventricles occurs as early as E14.5, and lineage-mapping revealed that the neuroepithelial cells in the conditional mutants are present, but fail to undergo normal differentiation at the stenotic site. Concomitant with a narrowing of the mutant third ventricle, we detected ectopic apoptosis, reduced proliferation, and abnormal β-catenin localization. Furthermore, consistent with the overlapping expression pattern of Pax3 and Pax7 in early cranial neuroepithelium, we demonstrated a combinatorial role, as compound Pax3/Pax7 heterozygotes display partially-penetrant congenital hydrocephalus. These murine data provide an experimental paradigm underpinning clinical observations of the presence of PAX3 mutations in some hydrocephalic patients. Full article

(This article belongs to the Special Issue Cell Fate Decisions in Development and Disease)

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Hermes (Rbpms) is a Critical Component of RNP Complexes that Sequester Germline RNAs during Oogenesis

by Tristan Aguero, Yi Zhou, Malgorzata Kloc, Patrick Chang, Evelyn Houliston and Mary Lou King

J. Dev. Biol. 2016, 4(1), 2; https://doi.org/10.3390/jdb4010002 - 19 Jan 2016

Cited by 18 | Viewed by 6586

Abstract

The germ cell lineage in Xenopus is specified by the inheritance of germ plasm that assembles within the mitochondrial cloud or Balbiani body in stage I oocytes. Specific RNAs, such as nanos1, localize to the germ plasm. nanos1 has the essential germline [...] Read more.

The germ cell lineage in Xenopus is specified by the inheritance of germ plasm that assembles within the mitochondrial cloud or Balbiani body in stage I oocytes. Specific RNAs, such as nanos1, localize to the germ plasm. nanos1 has the essential germline function of blocking somatic gene expression and thus preventing Primordial Germ Cell (PGC) loss and sterility. Hermes/Rbpms protein and nanos RNA co-localize within germinal granules, diagnostic electron dense particles found within the germ plasm. Previous work indicates that nanos accumulates within the germ plasm through a diffusion/entrapment mechanism. Here we show that Hermes/Rbpms interacts with nanos through sequence specific RNA localization signals found in the nanos-3′UTR. Importantly, Hermes/Rbpms specifically binds nanos, but not Vg1 RNA in the nucleus of stage I oocytes. In vitro binding data show that Hermes/Rbpms requires additional factors that are present in stage I oocytes in order to bind nanos1. One such factor may be hnRNP I, identified in a yeast-2-hybrid screen as directly interacting with Hermes/Rbpms. We suggest that Hermes/Rbpms functions as part of a RNP complex in the nucleus that facilitates selection of germline RNAs for germ plasm localization. We propose that Hermes/Rbpms is required for nanos RNA to form within the germinal granules and in this way, participates in the germline specific translational repression and sequestration of nanos RNA. Full article

(This article belongs to the Special Issue Cell Fate Decisions in Development and Disease)

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Pbx4 is Required for the Temporal Onset of Zebrafish Myocardial Differentiation

by Robert M. Kao, Joel G. Rurik, Gist H. Farr III, Xiu Rong Dong, Mark W. Majesky and Lisa Maves

J. Dev. Biol. 2015, 3(4), 93-111; https://doi.org/10.3390/jdb3040093 - 12 Nov 2015

Cited by 15 | Viewed by 7010

Abstract

Proper control of the temporal onset of cellular differentiation is critical for regulating cell lineage decisions and morphogenesis during development. Pbx homeodomain transcription factors have emerged as important regulators of cellular differentiation. We previously showed, by using antisense morpholino knockdown, that Pbx factors [...] Read more.

Proper control of the temporal onset of cellular differentiation is critical for regulating cell lineage decisions and morphogenesis during development. Pbx homeodomain transcription factors have emerged as important regulators of cellular differentiation. We previously showed, by using antisense morpholino knockdown, that Pbx factors are needed for the timely activation of myocardial differentiation in zebrafish. In order to gain further insight into the roles of Pbx factors in heart development, we show here that zebrafish pbx4 mutant embryos exhibit delayed onset of myocardial differentiation, such as delayed activation of tnnt2a expression in early cardiomyocytes in the anterior lateral plate mesoderm. We also observe delayed myocardial morphogenesis and dysmorphic patterning of the ventricle and atrium, consistent with our previous Pbx knock-down studies. In addition, we find that pbx4 mutant larvae have aberrant outflow tracts and defective expression of the proepicardial marker tbx18. Finally, we present evidence for Pbx expression in cardiomyocyte precursors as well as heterogeneous Pbx expression among the pan-cytokeratin-expressing proepicardial cells near the developing ventricle. In summary, our data show that Pbx4 is required for the proper temporal activation of myocardial differentiation and establish a basis for studying additional roles of Pbx factors in heart development. Full article

(This article belongs to the Special Issue Cell Fate Decisions in Development and Disease)

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Review

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Cell Fate Decisions During Breast Cancer Development

by Kayla Gross, Ania Wronski, Adam Skibinski, Sarah Phillips and Charlotte Kuperwasser

J. Dev. Biol. 2016, 4(1), 4; https://doi.org/10.3390/jdb4010004 - 22 Jan 2016

Cited by 20 | Viewed by 10079

Abstract

During the formation of breast cancer, many genes become altered as cells evolve progressively from normal to a pre-malignant to a malignant state of growth. How mutations in genes lead to specific subtypes of human breast cancer is only partially understood. Here we [...] Read more.

During the formation of breast cancer, many genes become altered as cells evolve progressively from normal to a pre-malignant to a malignant state of growth. How mutations in genes lead to specific subtypes of human breast cancer is only partially understood. Here we review how initial genetic or epigenetic alterations within mammary epithelial cells (MECs) can alter cell fate decisions and put pre-malignant cells on a path towards cancer development with specific phenotypes. Understanding the early stages of breast cancer initiation and progression and how normal developmental processes are hijacked during transformation has significant implications for improving early detection and prevention of breast cancer. In addition, insights gleaned from this understanding may also be important for developing subtype-specific treatment options. Full article

(This article belongs to the Special Issue Cell Fate Decisions in Development and Disease)

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Notochord Cells in Intervertebral Disc Development and Degeneration

by Matthew R. McCann and Cheryle A. Séguin

J. Dev. Biol. 2016, 4(1), 3; https://doi.org/10.3390/jdb4010003 - 21 Jan 2016

Cited by 81 | Viewed by 17456

Abstract

The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways [...] Read more.

The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. Full article

(This article belongs to the Special Issue Cell Fate Decisions in Development and Disease)

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Role of Chondrocytes in Cartilage Formation, Progression of Osteoarthritis and Cartilage Regeneration

by Hemanth Akkiraju and Anja Nohe

J. Dev. Biol. 2015, 3(4), 177-192; https://doi.org/10.3390/jdb3040177 - 18 Dec 2015

Cited by 285 | Viewed by 19462

Abstract

Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their [...] Read more.

Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their function leads to degenerative diseases like Osteoarthritis (OA). OA is characterized by cartilage degradation, osteophyte formation and stiffening of joints. Cartilage degeneration is a consequence of chondrocyte hypertrophy along with the expression of proteolytic enzymes. Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) are an example of these enzymes that degrade the ECM. Signaling cascades involved in limb patterning and cartilage repair play a role in OA progression. However, the regulation of these remains to be elucidated. Further the role of stem cells and mature chondrocytes in OA progression is unclear. The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term. However, many questions are unanswered such as the efficacy of MSCs usage in therapy. This review focuses on the role of chondrocytes in cartilage formation and the progression of OA. Moreover, it summarizes possible alternative therapeutic approaches using MSC infusion for cartilage restoration. Full article

(This article belongs to the Special Issue Cell Fate Decisions in Development and Disease)

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Cell Fate Decision Making through Oriented Cell Division

by Evan B. Dewey, Danielle T. Taylor and Christopher A. Johnston

J. Dev. Biol. 2015, 3(4), 129-157; https://doi.org/10.3390/jdb3040129 - 14 Dec 2015

Cited by 28 | Viewed by 8578

Abstract

The ability to dictate cell fate decisions is critical during animal development. Moreover, faithful execution of this process ensures proper tissue homeostasis throughout adulthood, whereas defects in the molecular machinery involved may contribute to disease. Evolutionarily conserved protein complexes control cell fate decisions [...] Read more.

The ability to dictate cell fate decisions is critical during animal development. Moreover, faithful execution of this process ensures proper tissue homeostasis throughout adulthood, whereas defects in the molecular machinery involved may contribute to disease. Evolutionarily conserved protein complexes control cell fate decisions across diverse tissues. Maintaining proper daughter cell inheritance patterns of these determinants during mitosis is therefore a fundamental step of the cell fate decision-making process. In this review, we will discuss two key aspects of this fate determinant segregation activity, cortical cell polarity and mitotic spindle orientation, and how they operate together to produce oriented cell divisions that ultimately influence daughter cell fate. Our focus will be directed at the principal underlying molecular mechanisms and the specific cell fate decisions they have been shown to control. Full article

(This article belongs to the Special Issue Cell Fate Decisions in Development and Disease)

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Pigment Epithelium-Derived Factor (PEDF) is a Determinant of Stem Cell Fate: Lessons from an Ultra-Rare Disease

by Usman Sagheer, Jingjing Gong and Chuhan Chung

J. Dev. Biol. 2015, 3(4), 112-128; https://doi.org/10.3390/jdb3040112 - 20 Nov 2015

Cited by 15 | Viewed by 7976

Abstract

PEDF is a secreted glycoprotein that is widely expressed by multiple organs. Numerous functional contributions have been attributed to PEDF with antiangiogenic, antitumor, anti-inflammatory, and neurotrophic properties among the most prominent. The discovery that null mutations in the PEDF gene results in Osteogenesis [...] Read more.

PEDF is a secreted glycoprotein that is widely expressed by multiple organs. Numerous functional contributions have been attributed to PEDF with antiangiogenic, antitumor, anti-inflammatory, and neurotrophic properties among the most prominent. The discovery that null mutations in the PEDF gene results in Osteogenesis Imperfecta Type VI, a rare autosomal recessive bone disease characterized by multiple fractures, highlights a critical developmental function for this protein. This ultra-rare orphan disease has provided biological insights into previous studies that noted PEDF’s effects on various stem cell populations. In addition to bone development, PEDF modulates resident stem cell populations in the brain, muscle, and eye. Functional effects on human embryonic stem cells have also been demonstrated. An overview of recent advances in our understanding by which PEDF regulates stem cells and their potential clinical applications will be evaluated in this review. Full article

(This article belongs to the Special Issue Cell Fate Decisions in Development and Disease)

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