Journal of Developmental Biology

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Open AccessArticle

Ttc21b Is Required in Bergmann Glia for Proper Granule Cell Radial Migration

by Ashley M. Driver, Christopher Shumrick and Rolf W. Stottmann

J. Dev. Biol. 2017, 5(4), 18; https://doi.org/10.3390/jdb5040018 - 19 Dec 2017

Cited by 10 | Viewed by 6008

Proper cerebellar development is dependent on tightly regulated proliferation, migration, and differentiation events. Disruptions in any of these leads to a range of cerebellar phenotypes from ataxia to childhood tumors. Animal models have shown that proper regulation of sonic hedgehog (Shh) [...] Read more.

Proper cerebellar development is dependent on tightly regulated proliferation, migration, and differentiation events. Disruptions in any of these leads to a range of cerebellar phenotypes from ataxia to childhood tumors. Animal models have shown that proper regulation of sonic hedgehog (Shh) signaling is crucial for normal cerebellar architecture, and increased signaling leads to cerebellar tumor formation. Primary cilia are known to be required for the proper regulation of multiple developmental signaling pathways, including Shh. Tetratricopeptide Repeat Domain 21B (Ttc21b) is required for proper primary cilia form and function, and is primarily thought to restrict Shh signaling. Here we investigated a role for Ttc21b in cerebellar development. Surprisingly, Ttc21b ablation in Bergmann glia resulted in the accumulation of ectopic granule cells in the lower/posterior lobes of the cerebellum and a reduction in Shh signaling. Ttc21b ablation in just Purkinje cells resulted in a similar phenotype seen in fewer cells, but across the entire extent of the cerebellum. These results suggest that Ttc21b expression is required for Bergmann glia structure and signaling in the developing cerebellum, and in some contexts, augments rather than attenuates Shh signaling. Full article

(This article belongs to the Special Issue Development of the Brain in Health and Disease)

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3253 KiB

Open AccessFeature PaperReview

The Role of Hedgehog Signalling in the Formation of the Ventricular Septum

by Antonia Wiegering, Ulrich Rüther and Christoph Gerhardt

J. Dev. Biol. 2017, 5(4), 17; https://doi.org/10.3390/jdb5040017 - 12 Dec 2017

Cited by 15 | Viewed by 11342

Abstract

An incomplete septation of the ventricles in the vertebrate heart that disturbes the strict separation between the contents of the two ventricles is termed a ventricular septal defect (VSD). Together with bicuspid aortic valves, it is the most frequent congenital heart disease in [...] Read more.

An incomplete septation of the ventricles in the vertebrate heart that disturbes the strict separation between the contents of the two ventricles is termed a ventricular septal defect (VSD). Together with bicuspid aortic valves, it is the most frequent congenital heart disease in humans. Until now, life-threatening VSDs are usually treated surgically. To avoid surgery and to develop an alternative therapy (e.g., a small molecule therapy), it is necessary to understand the molecular mechanisms underlying ventricular septum (VS) development. Consequently, various studies focus on the investigation of signalling pathways, which play essential roles in the formation of the VS. In the past decade, several reports found evidence for an involvement of Hedgehog (HH) signalling in VS development. In this review article, we will summarise the current knowledge about the association between HH signalling and VS formation and discuss the use of such knowledge to design treatment strategies against the development of VSDs. Full article

(This article belongs to the Collection Hedgehog Signaling in Embryogenesis)

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Open AccessReview

Engineering the Drosophila Genome for Developmental Biology

by Dagmara Korona, Stefan A. Koestler and Steven Russell

J. Dev. Biol. 2017, 5(4), 16; https://doi.org/10.3390/jdb5040016 - 11 Dec 2017

Cited by 11 | Viewed by 8384

Abstract

The recent development of transposon and CRISPR-Cas9-based tools for manipulating the fly genome in vivo promises tremendous progress in our ability to study developmental processes. Tools for introducing tags into genes at their endogenous genomic loci facilitate imaging or biochemistry approaches at the [...] Read more.

The recent development of transposon and CRISPR-Cas9-based tools for manipulating the fly genome in vivo promises tremendous progress in our ability to study developmental processes. Tools for introducing tags into genes at their endogenous genomic loci facilitate imaging or biochemistry approaches at the cellular or subcellular levels. Similarly, the ability to make specific alterations to the genome sequence allows much more precise genetic control to address questions of gene function. Full article

(This article belongs to the Collection Drosophila - A Model System for Developmental Biology)

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Open AccessReview

Drosophila as a Model to Study the Link between Metabolism and Cancer

by Héctor Herranz and Stephen M. Cohen

J. Dev. Biol. 2017, 5(4), 15; https://doi.org/10.3390/jdb5040015 - 1 Dec 2017

Cited by 21 | Viewed by 6899

Abstract

Cellular metabolism has recently been recognized as a hallmark of cancer. Investigating the origin and effects of the reprogrammed metabolism of tumor cells, and identifying its genetic mediators, will improve our understanding of how these changes contribute to disease progression and may suggest [...] Read more.

Cellular metabolism has recently been recognized as a hallmark of cancer. Investigating the origin and effects of the reprogrammed metabolism of tumor cells, and identifying its genetic mediators, will improve our understanding of how these changes contribute to disease progression and may suggest new approaches to therapy. Drosophila melanogaster is emerging as a valuable model to study multiple aspects of tumor formation and malignant transformation. In this review, we discuss the use of Drosophila as model to study how changes in cellular metabolism, as well as metabolic disease, contribute to cancer. Full article

(This article belongs to the Collection Drosophila - A Model System for Developmental Biology)

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Open AccessFeature PaperReview

The Hedgehog Signaling Pathway Emerges as a Pathogenic Target

by Margery G. Smelkinson

J. Dev. Biol. 2017, 5(4), 14; https://doi.org/10.3390/jdb5040014 - 28 Nov 2017

Cited by 36 | Viewed by 8789

Abstract

The Hedgehog (Hh) signaling pathway plays an essential role in the growth, development, and homeostatis of many tissues in vertebrates and invertebrates. Much of what is known about Hh signaling is in the context of embryonic development and tumor formation. However, a growing [...] Read more.

The Hedgehog (Hh) signaling pathway plays an essential role in the growth, development, and homeostatis of many tissues in vertebrates and invertebrates. Much of what is known about Hh signaling is in the context of embryonic development and tumor formation. However, a growing body of evidence is emerging indicating that Hh signaling is also involved in postnatal processes such as tissue repair and adult immune responses. To that extent, Hh signaling has also been shown to be a target for some pathogens that presumably utilize the pathway to control the local infected environment. In this review, we discuss what is currently known regarding pathogenic interactions with Hh signaling and speculate on the reasons for this pathway being a target. We also hope to shed light on the possibility of using small molecule modulators of Hh signaling as effective therapies for a wider range of human diseases beyond their current use in a limited number of cancers. Full article

(This article belongs to the Collection Hedgehog Signaling in Embryogenesis)

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Open AccessFeature PaperReview

Emerging Roles of DYRK Kinases in Embryogenesis and Hedgehog Pathway Control

by Rajeev Singh and Matthias Lauth

J. Dev. Biol. 2017, 5(4), 13; https://doi.org/10.3390/jdb5040013 - 21 Nov 2017

Cited by 24 | Viewed by 7775

Abstract

Hedgehog (Hh)/GLI signaling is an important instructive cue in various processes during embryonic development, such as tissue patterning, stem cell maintenance, and cell differentiation. It also plays crucial roles in the development of many pediatric and adult malignancies. Understanding the molecular mechanisms of [...] Read more.

Hedgehog (Hh)/GLI signaling is an important instructive cue in various processes during embryonic development, such as tissue patterning, stem cell maintenance, and cell differentiation. It also plays crucial roles in the development of many pediatric and adult malignancies. Understanding the molecular mechanisms of pathway regulation is therefore of high interest. Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) comprise a group of protein kinases which are emerging modulators of signal transduction, cell proliferation, survival, and cell differentiation. Work from the last years has identified a close regulatory connection between DYRKs and the Hh signaling system. In this manuscript, we outline the mechanistic influence of DYRK kinases on Hh signaling with a focus on the mammalian situation. We furthermore aim to bring together what is known about the functional consequences of a DYRK-Hh cross-talk and how this might affect cellular processes in development, physiology, and pathology. Full article

(This article belongs to the Collection Hedgehog Signaling in Embryogenesis)

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Roles of the Hedgehog Signaling Pathway in Epidermal and Hair Follicle Development, Homeostasis, and Cancer

by Yoshinori Abe and Nobuyuki Tanaka

J. Dev. Biol. 2017, 5(4), 12; https://doi.org/10.3390/jdb5040012 - 20 Nov 2017

Cited by 65 | Viewed by 17979

Abstract

The epidermis is the outermost layer of the skin and provides a protective barrier against environmental insults. It is a rapidly-renewing tissue undergoing constant regeneration, maintained by several types of stem cells. The Hedgehog (HH) signaling pathway is one of the fundamental signaling [...] Read more.

The epidermis is the outermost layer of the skin and provides a protective barrier against environmental insults. It is a rapidly-renewing tissue undergoing constant regeneration, maintained by several types of stem cells. The Hedgehog (HH) signaling pathway is one of the fundamental signaling pathways that contributes to epidermal development, homeostasis, and repair, as well as to hair follicle development and follicle bulge stem cell maintenance. The HH pathway interacts with other signal transduction pathways, including those activated by Wnt, bone morphogenetic protein, platelet-derived growth factor, Notch, and ectodysplasin. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important for elucidating fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in the development and homeostasis epidermis and hair follicles, and in basal cell carcinoma formation, providing an update of current knowledge in this field. Full article

(This article belongs to the Collection Hedgehog Signaling in Embryogenesis)

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Contributions of Noncanonical Smoothened Signaling During Embryonic Development

by Tanushree Pandit and Stacey K. Ogden

J. Dev. Biol. 2017, 5(4), 11; https://doi.org/10.3390/jdb5040011 - 17 Oct 2017

Cited by 17 | Viewed by 5840

Abstract

The Sonic Hedgehog (Shh) signaling pathway is active during embryonic development in metazoans, and provides instructional cues necessary for proper tissue patterning. The pathway signal transducing component, Smoothened (Smo), is a G protein-coupled receptor (GPCR) that has been demonstrated to signal through at [...] Read more.

The Sonic Hedgehog (Shh) signaling pathway is active during embryonic development in metazoans, and provides instructional cues necessary for proper tissue patterning. The pathway signal transducing component, Smoothened (Smo), is a G protein-coupled receptor (GPCR) that has been demonstrated to signal through at least two effector routes. The first is a G protein–independent canonical route that signals to Gli transcriptional effectors to establish transcriptional programs specifying cell fate during early embryonic development. The second, commonly referred to as the noncanonical Smo signal, induces rapid, transcription-independent responses that are essential for establishing and maintaining distinct cell behaviors during development. Herein, we discuss contributions of this noncanonical route during embryonic development. We also highlight important open questions regarding noncanonical Smo signal route selection during development, and consider implications of noncanonical signal corruption in disease. Full article

(This article belongs to the Collection Hedgehog Signaling in Embryogenesis)

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4570 KiB

Open AccessArticle

The Roles of the Wnt-Antagonists Axin and Lrp4 during Embryogenesis of the Red Flour Beetle Tribolium castaneum

by Romy Prühs, Anke Beermann and Reinhard Schröder

J. Dev. Biol. 2017, 5(4), 10; https://doi.org/10.3390/jdb5040010 - 15 Oct 2017

Cited by 14 | Viewed by 8099

Abstract

In both vertebrates and invertebrates, the Wnt-signaling pathway is essential for numerous processes in embryogenesis and during adult life. Wnt activity is fine-tuned at various levels by the interplay of a number of Wnt-agonists (Wnt ligands, Frizzled-receptors, Lrp5/6 coreceptors) and Wnt-antagonists (among them [...] Read more.

In both vertebrates and invertebrates, the Wnt-signaling pathway is essential for numerous processes in embryogenesis and during adult life. Wnt activity is fine-tuned at various levels by the interplay of a number of Wnt-agonists (Wnt ligands, Frizzled-receptors, Lrp5/6 coreceptors) and Wnt-antagonists (among them Axin, Secreted frizzled and Lrp4) to define anterior–posterior polarity of the early embryo and specify cell fate in organogenesis. So far, the functional analysis of Wnt-pathway components in insects has concentrated on the roles of Wnt-agonists and on the Wnt-antagonist Axin. We depict here additional features of the Wnt-antagonist Axin in the flour beetle Tribolium castaneum. We show that Tc-axin is dynamically expressed throughout embryogenesis and confirm its essential role in head development. In addition, we describe an as yet undetected, more extreme Tc-axin RNAi-phenotype, the ectopic formation of posterior abdominal segments in reverse polarity and a second hindgut at the anterior. For the first time, we describe here that an lrp4 ortholog is involved in axis formation in an insect. The Tribolium Lrp4 ortholog is ubiquitously expressed throughout embryogenesis. Its downregulation via maternal RNAi results in the reduction of head structures but not in axis polarity reversal. Furthermore, segmentation is impaired and larvae develop with a severe gap-phenotype. We conclude that, as in vertebrates, Tc-lrp4 functions as a Wnt-inhibitor in Tribolium during various stages of embryogenesis. We discuss the role of both components as negative modulators of Wnt signaling in respect to axis formation and segmentation in Tribolium. Full article

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J. Dev. Biol., Volume 5, Issue 4 (December 2017) – 9 articles

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