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Biomolecules
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Cell Type- and Context-Specific Roles and Regulation of Notch Signaling
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Cell Type- and Context-Specific Roles and Regulation of Notch Signaling

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 34590

Special Issue Editor

Dr. Hamed Jafar-Nejad

E-Mail Website
Guest Editor
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Interests: glycosylation; N-glycanase 1; Notch signaling; BMP signaling; AMPK signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Notch signaling is an evolutionarily conserved intercellular signaling mechanism that plays important roles in the embryonic development and adult homeostasis of animals, and in human disease. The Notch pathway is used so broadly that it is difficult to identify cell types or developmental processes that are not regulated by Notch signaling. Moreover, a growing list of human diseases affecting multiple organ systems have been identified that are either caused by mutations in the Notch pathway components or whose pathogenesis and/or progression are affected by alterations in the level of Notch pathway activity. Notably, mutations in each Notch pathway receptor/ligand result in specific phenotypes that are at least partially non-overlapping with the mutant phenotypes of other pathway components. In line with the above-mentioned observations, the rather simple design of the Notch pathway, and the limited number of its core components, multiple regulatory mechanisms exist to make the Notch pathway such a versatile signaling pathway. This Special Issue intends to provide examples of exciting work on such regulatory mechanisms. Areas of particular interest include, but are not limited to, the regulation of Notch signaling by post-translational modifications; the role of Notch signaling in the development, homeostasis, and diseases of specific organ systems; biophysical and structural factors affecting Notch pathway activation; non-canonical forms of Notch signaling; and therapeutic approaches targeting the Notch pathway.

We look forward to reading your contributions.

Dr. Hamed Jafar-Nejad
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Animal models
  • Biophysical mechanisms
  • Developmental mechanisms
  • Intercellular trafficking
  • Mechanisms for genetic disorders
  • Notch signaling
  • Post-translational modification
  • Receptor-ligand interactions
  • Structural biology
  • Targeted therapies

Published Papers (5 papers)

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Review

17 pages, 1176 KiB  
Review
Notch3 in Development, Health and Disease
by Samira Hosseini-Alghaderi and Martin Baron
Biomolecules 2020, 10(3), 485; https://doi.org/10.3390/biom10030485 - 23 Mar 2020
Cited by 39 | Viewed by 9077
Abstract
Notch3 is one of four mammalian Notch proteins, which act as signalling receptors to control cell fate in many developmental and adult tissue contexts. Notch signalling continues to be important in the adult organism for tissue maintenance and renewal and mis-regulation of Notch [...] Read more.
Notch3 is one of four mammalian Notch proteins, which act as signalling receptors to control cell fate in many developmental and adult tissue contexts. Notch signalling continues to be important in the adult organism for tissue maintenance and renewal and mis-regulation of Notch is involved in many diseases. Genetic studies have shown that Notch3 gene knockouts are viable and have limited developmental defects, focussed mostly on defects in the arterial smooth muscle cell lineage. Additional studies have revealed overlapping roles for Notch3 with other Notch proteins, which widen the range of developmental functions. In the adult, Notch3, in collaboration with other Notch proteins, is involved in stem cell regulation in different tissues in stem cell regulation in different tissues, and it also controls the plasticity of the vascular smooth muscle phenotype involved in arterial vessel remodelling. Overexpression, gene amplification and mis-activation of Notch3 are associated with different cancers, in particular triple negative breast cancer and ovarian cancer. Mutations of Notch3 are associated with a dominantly inherited disease CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), and there is further evidence linking Notch3 misregulation to hypertensive disease. Here we discuss the distinctive roles of Notch3 in development, health and disease, different views as to the underlying mechanisms of its activation and misregulation in different contexts and potential for therapeutic intervention. Full article
(This article belongs to the Special Issue Cell Type- and Context-Specific Roles and Regulation of Notch Signaling)
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18 pages, 600 KiB  
Review
Hear, Hear for Notch: Control of Cell Fates in the Inner Ear by Notch Signaling
by Rogers Brown and Andrew K. Groves
Biomolecules 2020, 10(3), 370; https://doi.org/10.3390/biom10030370 - 28 Feb 2020
Cited by 26 | Viewed by 4854
Abstract
The vertebrate inner ear is responsible for detecting sound, gravity, and head motion. These mechanical forces are detected by mechanosensitive hair cells, arranged in a series of sensory patches in the vestibular and cochlear regions of the ear. Hair cells form synapses with [...] Read more.
The vertebrate inner ear is responsible for detecting sound, gravity, and head motion. These mechanical forces are detected by mechanosensitive hair cells, arranged in a series of sensory patches in the vestibular and cochlear regions of the ear. Hair cells form synapses with neurons of the VIIIth cranial ganglion, which convey sound and balance information to the brain. They are surrounded by supporting cells, which nourish and protect the hair cells, and which can serve as a source of stem cells to regenerate hair cells after damage in non-mammalian vertebrates. The Notch signaling pathway plays many roles in the development of the inner ear, from the earliest formation of future inner ear ectoderm on the side of the embryonic head, to regulating the production of supporting cells, hair cells, and the neurons that innervate them. Notch signaling is re-deployed in non-mammalian vertebrates during hair cell regeneration, and attempts have been made to manipulate the Notch pathway to promote hair cell regeneration in mammals. In this review, we summarize the different modes of Notch signaling in inner ear development and regeneration, and describe how they interact with other signaling pathways to orchestrate the fine-grained cellular patterns of the ear. Full article
(This article belongs to the Special Issue Cell Type- and Context-Specific Roles and Regulation of Notch Signaling)
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18 pages, 808 KiB  
Review
Notch Signaling in Skeletal Development, Homeostasis and Pathogenesis
by Jennifer T. Zieba, Yi-Ting Chen, Brendan H. Lee and Yangjin Bae
Biomolecules 2020, 10(2), 332; https://doi.org/10.3390/biom10020332 - 19 Feb 2020
Cited by 47 | Viewed by 5473
Abstract
Skeletal development is a complex process which requires the tight regulation of gene activation and suppression in response to local signaling pathways. Among these pathways, Notch signaling is implicated in governing cell fate determination, proliferation, differentiation and apoptosis of skeletal cells-osteoblasts, osteoclasts, osteocytes [...] Read more.
Skeletal development is a complex process which requires the tight regulation of gene activation and suppression in response to local signaling pathways. Among these pathways, Notch signaling is implicated in governing cell fate determination, proliferation, differentiation and apoptosis of skeletal cells-osteoblasts, osteoclasts, osteocytes and chondrocytes. Moreover, human genetic mutations in Notch components emphasize the critical roles of Notch signaling in skeletal development and homeostasis. In this review, we focus on the physiological roles of Notch signaling in skeletogenesis, postnatal bone and cartilage homeostasis and fracture repair. We also discuss the pathological gain- and loss-of-function of Notch signaling in bone and cartilage, resulting in osteosarcoma and age-related degenerative diseases, such as osteoporosis and osteoarthritis. Understanding the physiological and pathological function of Notch signaling in skeletal tissues using animal models and human genetics will provide new insights into disease pathogenesis and offer novel approaches for the treatment of bone/cartilage diseases. Full article
(This article belongs to the Special Issue Cell Type- and Context-Specific Roles and Regulation of Notch Signaling)
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23 pages, 2097 KiB  
Review
Notch Signaling in Kidney Development, Maintenance, and Disease
by Malini Mukherjee, Eric Fogarty, Madhusudhana Janga and Kameswaran Surendran
Biomolecules 2019, 9(11), 692; https://doi.org/10.3390/biom9110692 - 04 Nov 2019
Cited by 43 | Viewed by 6919
Abstract
Kidney development involves formation of nephrons intricately aligned with the vasculature and connected to a branched network of collecting ducts. Notch signaling plays multiple roles during kidney development involving the formation of nephrons composed of diverse epithelial cell types arranged into tubular segments, [...] Read more.
Kidney development involves formation of nephrons intricately aligned with the vasculature and connected to a branched network of collecting ducts. Notch signaling plays multiple roles during kidney development involving the formation of nephrons composed of diverse epithelial cell types arranged into tubular segments, all the while maintaining a nephron progenitor niche. Here, we review the roles of Notch signaling identified from rodent kidney development and injury studies, while discussing human kidney diseases associated with aberrant Notch signaling. We also review Notch signaling requirement in maintenance of mature kidney epithelial cell states and speculate that Notch activity regulation mediates certain renal physiologic adaptations. Full article
(This article belongs to the Special Issue Cell Type- and Context-Specific Roles and Regulation of Notch Signaling)
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20 pages, 3272 KiB  
Review
The Roles of Notch Signaling in Liver Development and Disease
by Joshua M. Adams and Hamed Jafar-Nejad
Biomolecules 2019, 9(10), 608; https://doi.org/10.3390/biom9100608 - 14 Oct 2019
Cited by 59 | Viewed by 7664
Abstract
The Notch signaling pathway plays major roles in organ development across animal species. In the mammalian liver, Notch has been found critical in development, regeneration and disease. In this review, we highlight the major advances in our understanding of the role of Notch [...] Read more.
The Notch signaling pathway plays major roles in organ development across animal species. In the mammalian liver, Notch has been found critical in development, regeneration and disease. In this review, we highlight the major advances in our understanding of the role of Notch activity in proper liver development and function. Specifically, we discuss the latest discoveries on how Notch, in conjunction with other signaling pathways, aids in proper liver development, regeneration and repair. In addition, we review the latest in the role of Notch signaling in the pathogenesis of liver fibrosis and chronic liver disease. Finally, recent evidence has shed light on the emerging connection between Notch signaling and glucose and lipid metabolism. We hope that highlighting the major advances in the roles of Notch signaling in the liver will stimulate further research in this exciting field and generate additional ideas for therapeutic manipulation of the Notch pathway in liver diseases. Full article
(This article belongs to the Special Issue Cell Type- and Context-Specific Roles and Regulation of Notch Signaling)
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