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J. Dev. Biol., Volume 9, Issue 1 (March 2021) – 11 articles

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Review
Expanding the Junction: New Insights into Non-Occluding Roles for Septate Junction Proteins during Development
J. Dev. Biol. 2021, 9(1), 11; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010011 - 21 Mar 2021
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Abstract
The septate junction (SJ) provides an occluding function for epithelial tissues in invertebrate organisms. This ability to seal the paracellular route between cells allows internal tissues to create unique compartments for organ function and endows the epidermis with a barrier function to restrict [...] Read more.
The septate junction (SJ) provides an occluding function for epithelial tissues in invertebrate organisms. This ability to seal the paracellular route between cells allows internal tissues to create unique compartments for organ function and endows the epidermis with a barrier function to restrict the passage of pathogens. Over the past twenty-five years, numerous investigators have identified more than 30 proteins that are required for the formation or maintenance of the SJs in Drosophila melanogaster, and have determined many of the steps involved in the biogenesis of the junction. Along the way, it has become clear that SJ proteins are also required for a number of developmental events that occur throughout the life of the organism. Many of these developmental events occur prior to the formation of the occluding junction, suggesting that SJ proteins possess non-occluding functions. In this review, we will describe the composition of SJs, taking note of which proteins are core components of the junction versus resident or accessory proteins, and the steps involved in the biogenesis of the junction. We will then elaborate on the functions that core SJ proteins likely play outside of their role in forming the occluding junction and describe studies that provide some cell biological perspectives that are beginning to provide mechanistic understanding of how these proteins function in developmental contexts. Full article
(This article belongs to the Special Issue Cell Adhesion Molecules in Development)
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Review
Metabolism in the Zebrafish Retina
J. Dev. Biol. 2021, 9(1), 10; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010010 - 15 Mar 2021
Cited by 1 | Viewed by 984
Abstract
Retinal photoreceptors are amongst the most metabolically active cells in the body, consuming more glucose as a metabolic substrate than even the brain. This ensures that there is sufficient energy to establish and maintain photoreceptor functions during and after their differentiation. Such high [...] Read more.
Retinal photoreceptors are amongst the most metabolically active cells in the body, consuming more glucose as a metabolic substrate than even the brain. This ensures that there is sufficient energy to establish and maintain photoreceptor functions during and after their differentiation. Such high dependence on glucose metabolism is conserved across vertebrates, including zebrafish from early larval through to adult retinal stages. As the zebrafish retina develops rapidly, reaching an adult-like structure by 72 hours post fertilisation, zebrafish larvae can be used to study metabolism not only during retinogenesis, but also in functionally mature retinae. The interplay between rod and cone photoreceptors and the neighbouring retinal pigment epithelium (RPE) cells establishes a metabolic ecosystem that provides essential control of their individual functions, overall maintaining healthy vision. The RPE facilitates efficient supply of glucose from the choroidal vasculature to the photoreceptors, which produce metabolic products that in turn fuel RPE metabolism. Many inherited retinal diseases (IRDs) result in photoreceptor degeneration, either directly arising from photoreceptor-specific mutations or secondary to RPE loss, leading to sight loss. Evidence from a number of vertebrate studies suggests that the imbalance of the metabolic ecosystem in the outer retina contributes to metabolic failure and disease pathogenesis. The use of larval zebrafish mutants with disease-specific mutations that mirror those seen in human patients allows us to uncover mechanisms of such dysregulation and disease pathology with progression from embryonic to adult stages, as well as providing a means of testing novel therapeutic approaches. Full article
(This article belongs to the Special Issue Women in Developmental Biology)
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Review
Conservation and Innovation: Versatile Roles for LRP4 in Nervous System Development
J. Dev. Biol. 2021, 9(1), 9; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010009 - 14 Mar 2021
Cited by 1 | Viewed by 1021
Abstract
As the nervous system develops, connections between neurons must form to enable efficient communication. This complex process of synaptic development requires the coordination of a series of intricate mechanisms between partner neurons to ensure pre- and postsynaptic differentiation. Many of these mechanisms employ [...] Read more.
As the nervous system develops, connections between neurons must form to enable efficient communication. This complex process of synaptic development requires the coordination of a series of intricate mechanisms between partner neurons to ensure pre- and postsynaptic differentiation. Many of these mechanisms employ transsynaptic signaling via essential secreted factors and cell surface receptors to promote each step of synaptic development. One such cell surface receptor, LRP4, has emerged as a synaptic organizer, playing a critical role in conveying extracellular signals to initiate diverse intracellular events during development. To date, LRP4 is largely known for its role in development of the mammalian neuromuscular junction, where it functions as a receptor for the synaptogenic signal Agrin to regulate synapse development. Recently however, LRP4 has emerged as a synapse organizer in the brain, where new functions for the protein continue to arise, adding further complexity to its already versatile roles. Additional findings indicate that LRP4 plays a role in disorders of the nervous system, including myasthenia gravis, amyotrophic lateral sclerosis, and Alzheimer’s disease, demonstrating the need for further study to understand disease etiology. This review will highlight our current knowledge of how LRP4 functions in the nervous system, focusing on the diverse developmental roles and different modes this essential cell surface protein uses to ensure the formation of robust synaptic connections. Full article
(This article belongs to the Special Issue Cell Adhesion Molecules in Development)
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Article
Timing of Mouse Molar Formation Is Independent of Jaw Length Including Retromolar Space
J. Dev. Biol. 2021, 9(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010008 - 12 Mar 2021
Viewed by 598
Abstract
For humans and other mammals to eat effectively, teeth must develop properly inside the jaw. Deciphering craniodental integration is central to explaining the timely formation of permanent molars, including third molars which are often impacted in humans, and to clarifying how teeth and [...] Read more.
For humans and other mammals to eat effectively, teeth must develop properly inside the jaw. Deciphering craniodental integration is central to explaining the timely formation of permanent molars, including third molars which are often impacted in humans, and to clarifying how teeth and jaws fit, function and evolve together. A factor long-posited to influence molar onset time is the jaw space available for each molar organ to form within. Here, we tested whether each successive molar initiates only after a minimum threshold of space is created via jaw growth. We used synchrotron-based micro-CT scanning to assess developing molars in situ within jaws of C57BL/6J mice aged E10 to P32, encompassing molar onset to emergence. We compared total jaw, retromolar and molar lengths, and molar onset times, between upper and lower jaws. Initiation time and developmental duration were comparable between molar upper and lower counterparts despite shorter, slower-growing retromolar space in the upper jaw, and despite size differences between upper and lower molars. Timing of molar formation appears unmoved by jaw length including space. Conditions within the dental lamina likely influence molar onset much more than surrounding jaw tissues. We theorize that molar initiation is contingent on sufficient surface area for the physical reorganization of dental epithelium and its invagination of underlying mesenchyme. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
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Article
The Collagens DPY-17 and SQT-3 Direct Anterior–Posterior Migration of the Q Neuroblasts in C. elegans
J. Dev. Biol. 2021, 9(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010007 - 19 Feb 2021
Viewed by 913
Abstract
Cell adhesion molecules and their extracellular ligands control morphogenetic events such as directed cell migration. The migration of neuroblasts and neural crest cells establishes the structure of the central and peripheral nervous systems. In C. elegans, the bilateral Q neuroblasts and their [...] Read more.
Cell adhesion molecules and their extracellular ligands control morphogenetic events such as directed cell migration. The migration of neuroblasts and neural crest cells establishes the structure of the central and peripheral nervous systems. In C. elegans, the bilateral Q neuroblasts and their descendants undergo long-range migrations with left/right asymmetry. QR and its descendants on the right migrate anteriorly, and QL and its descendants on the left migrate posteriorly, despite identical patterns of cell division, cell death, and neuronal generation. The initial direction of protrusion of the Q cells relies on the left/right asymmetric functions of the transmembrane receptors UNC-40/DCC and PTP-3/LAR in the Q cells. Here, we show that Q cell left/right asymmetry of migration is independent of the GPA-16/Gα pathway which regulates other left/right asymmetries, including nervous system L/R asymmetry. No extracellular cue has been identified that guides initial Q anterior versus posterior migrations. We show that collagens DPY-17 and SQT-3 control initial Q direction of protrusion. Genetic interactions with UNC-40/DCC and PTP-3/LAR suggest that DPY-17 and SQT-3 drive posterior migration and might act with both receptors or in a parallel pathway. Analysis of mutants in other collagens and extracellular matrix components indicated that general perturbation of collagens and the extracellular matrix (ECM) did not result in directional defects, and that the effect of DPY-17 and SQT-3 on Q direction is specific. DPY-17 and SQT-3 are components of the cuticle, but a role in the basement membrane cannot be excluded. Possibly, DPY-17 and SQT-3 are part of a pattern in the cuticle and/or basement membrane that is oriented to the anterior–posterior axis of the animal and that is deciphered by the Q cells in a left–right asymmetric fashion. Alternatively, DPY-17 and SQT-3 might be involved in the production or stabilization of a guidance cue that directs Q migrations. In any case, these results describe a novel role for the DPY-17 and SQT-3 collagens in directing posterior Q neuroblast migration. Full article
(This article belongs to the Special Issue Cell Adhesion Molecules in Development)
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Article
Genome-Wide Binding Analyses of HOXB1 Revealed a Novel DNA Binding Motif Associated with Gene Repression
J. Dev. Biol. 2021, 9(1), 6; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010006 - 03 Feb 2021
Cited by 1 | Viewed by 728
Abstract
Knowledge of the diverse DNA binding specificities of transcription factors is important for understanding their specific regulatory functions in animal development and evolution. We have examined the genome-wide binding properties of the mouse HOXB1 protein in embryonic stem cells differentiated into neural fates. [...] Read more.
Knowledge of the diverse DNA binding specificities of transcription factors is important for understanding their specific regulatory functions in animal development and evolution. We have examined the genome-wide binding properties of the mouse HOXB1 protein in embryonic stem cells differentiated into neural fates. Unexpectedly, only a small number of HOXB1 bound regions (7%) correlate with binding of the known HOX cofactors PBX and MEIS. In contrast, 22% of the HOXB1 binding peaks display co-occupancy with the transcriptional repressor REST. Analyses revealed that co-binding of HOXB1 with PBX correlates with active histone marks and high levels of expression, while co-occupancy with REST correlates with repressive histone marks and repression of the target genes. Analysis of HOXB1 bound regions uncovered enrichment of a novel 15 base pair HOXB1 binding motif HB1RE (HOXB1 response element). In vitro template binding assays showed that HOXB1, PBX1, and MEIS can bind to this motif. In vivo, this motif is sufficient for direct expression of a reporter gene and over-expression of HOXB1 selectively represses this activity. Our analyses suggest that HOXB1 has evolved an association with REST in gene regulation and the novel HB1RE motif contributes to HOXB1 function in part through a repressive role in gene expression. Full article
(This article belongs to the Special Issue 2020 Feature Papers by JDB’ Editorial Board Members)
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Review
Altered Cogs of the Clock: Insights into the Embryonic Etiology of Spondylocostal Dysostosis
J. Dev. Biol. 2021, 9(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010005 - 29 Jan 2021
Viewed by 1036
Abstract
Spondylocostal dysostosis (SCDO) is a rare heritable congenital condition, characterized by multiple severe malformations of the vertebrae and ribs. Great advances were made in the last decades at the clinical level, by identifying the genetic mutations underlying the different forms of the disease. [...] Read more.
Spondylocostal dysostosis (SCDO) is a rare heritable congenital condition, characterized by multiple severe malformations of the vertebrae and ribs. Great advances were made in the last decades at the clinical level, by identifying the genetic mutations underlying the different forms of the disease. These were matched by extraordinary findings in the Developmental Biology field, which elucidated the cellular and molecular mechanisms involved in embryo body segmentation into the precursors of the axial skeleton. Of particular relevance was the discovery of the somitogenesis molecular clock that controls the progression of somite boundary formation over time. An overview of these concepts is presented, including the evidence obtained from animal models on the embryonic origins of the mutant-dependent disease. Evidence of an environmental contribution to the severity of the disease is discussed. Finally, a brief reference is made to emerging in vitro models of human somitogenesis which are being employed to model the molecular and cellular events occurring in SCDO. These represent great promise for understanding this and other human diseases and for the development of more efficient therapeutic approaches. Full article
(This article belongs to the Special Issue Advances in Development: Focus on Rare Congenital Diseases)
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Editorial
Acknowledgment to Reviewers of JDB in 2020
J. Dev. Biol. 2021, 9(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010004 - 29 Jan 2021
Viewed by 512
Abstract
Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that JDB maintains its standards for the high quality of its published papers [...] Full article
Review
The Skull’s Girder: A Brief Review of the Cranial Base
J. Dev. Biol. 2021, 9(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010003 - 23 Jan 2021
Viewed by 784
Abstract
The cranial base is a multifunctional bony platform within the core of the cranium, spanning rostral to caudal ends. This structure provides support for the brain and skull vault above, serves as a link between the head and the vertebral column below, and [...] Read more.
The cranial base is a multifunctional bony platform within the core of the cranium, spanning rostral to caudal ends. This structure provides support for the brain and skull vault above, serves as a link between the head and the vertebral column below, and seamlessly integrates with the facial skeleton at its rostral end. Unique from the majority of the cranial skeleton, the cranial base develops from a cartilage intermediate—the chondrocranium—through the process of endochondral ossification. Owing to the intimate association of the cranial base with nearly all aspects of the head, congenital birth defects impacting these structures often coincide with anomalies of the cranial base. Despite this critical importance, studies investigating the genetic control of cranial base development and associated disorders lags in comparison to other craniofacial structures. Here, we highlight and review developmental and genetic aspects of the cranial base, including its transition from cartilage to bone, dual embryological origins, and vignettes of transcription factors controlling its formation. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
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Review
Study of Natural Longlife Juvenility and Tissue Regeneration in Caudate Amphibians and Potential Application of Resulting Data in Biomedicine
J. Dev. Biol. 2021, 9(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010002 - 18 Jan 2021
Cited by 2 | Viewed by 889
Abstract
The review considers the molecular, cellular, organismal, and ontogenetic properties of Urodela that exhibit the highest regenerative abilities among tetrapods. The genome specifics and the expression of genes associated with cell plasticity are analyzed. The simplification of tissue structure is shown using the [...] Read more.
The review considers the molecular, cellular, organismal, and ontogenetic properties of Urodela that exhibit the highest regenerative abilities among tetrapods. The genome specifics and the expression of genes associated with cell plasticity are analyzed. The simplification of tissue structure is shown using the examples of the sensory retina and brain in mature Urodela. Cells of these and some other tissues are ready to initiate proliferation and manifest the plasticity of their phenotype as well as the correct integration into the pre-existing or de novo forming tissue structure. Without excluding other factors that determine regeneration, the pedomorphosis and juvenile properties, identified on different levels of Urodele amphibians, are assumed to be the main explanation for their high regenerative abilities. These properties, being fundamental for tissue regeneration, have been lost by amniotes. Experiments aimed at mammalian cell rejuvenation currently use various approaches. They include, in particular, methods that use secretomes from regenerating tissues of caudate amphibians and fish for inducing regenerative responses of cells. Such an approach, along with those developed on the basis of knowledge about the molecular and genetic nature and age dependence of regeneration, may become one more step in the development of regenerative medicine Full article
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Article
Sas-4 Colocalizes with the Ciliary Rootlets of the Drosophila Sensory Organs
J. Dev. Biol. 2021, 9(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010001 - 05 Jan 2021
Viewed by 785
Abstract
The Drosophila eye displays peculiar sensory organs of unknown function, the mechanosensory bristles, that are intercalated among the adjacent ommatidia. Like the other Drosophila sensory organs, the mechanosensory bristles consist of a bipolar neuron and two tandemly aligned centrioles, the distal of which [...] Read more.
The Drosophila eye displays peculiar sensory organs of unknown function, the mechanosensory bristles, that are intercalated among the adjacent ommatidia. Like the other Drosophila sensory organs, the mechanosensory bristles consist of a bipolar neuron and two tandemly aligned centrioles, the distal of which nucleates the ciliary axoneme and represents the starting point of the ciliary rootlets. We report here that the centriole associated protein Sas-4 colocalizes with the short ciliary rootlets of the mechanosensory bristles and with the elongated rootlets of chordotonal and olfactory neurons. This finding suggests an unexpected cytoplasmic localization of Sas-4 protein and points to a new underscored role for this protein. Moreover, we observed that the sheath cells associated with the sensory neurons also display two tandemly aligned centrioles but lacks ciliary axonemes, suggesting that the dendrites of the sensory neurons are dispensable for the assembly of aligned centrioles and rootlets. Full article
(This article belongs to the Special Issue Cilia in Development)
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