2021 Feature Papers by JDB’s Editorial Board Members

A special issue of Journal of Developmental Biology (ISSN 2221-3759).

Deadline for manuscript submissions: closed (15 November 2021) | Viewed by 23409

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Herman B Wells Center for Pediatric Research, 1044 West Walnut Street, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Interests: birth defects; developmental basis of congenital and acquired cardiopulmonary diseases; neonatal lung alveolar septation; transgenic mouse modelling; cell lineage tracing; neural crest; fibroblast-to-myofibroblast transition; extracellular matrix
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Special Issue Information

Dear Colleagues,

This Special Issue on “2021 Feature Papers by JDB’s Editorial Board Members” represents a collection of papers submitted exclusively by its Editorial Board Members (EBMs), as well as invited papers from relevant experts. By representing different areas of research on developmental biology conducted in the laboratories, this Special Issue shall introduce JDB as a first-class platform for reporting scientific data.

Authors can submit their manuscripts online at www.mdpi.com by registering and logging in the following website: https://susy.mdpi.com/user/login. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the Special Issue website.

Prof. Simon J. Conway
Guest Editor

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Published Papers (7 papers)

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Research

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16 pages, 3137 KiB  
Article
The Hippo Pathway Effectors YAP/TAZ Are Essential for Mineralized Tissue Homeostasis in the Alveolar Bone/Periodontal Complex
by Mirali Pandya, Gokul Gopinathan, Connie Tillberg, Jun Wang, Xianghong Luan and Thomas G. H. Diekwisch
J. Dev. Biol. 2022, 10(1), 14; https://doi.org/10.3390/jdb10010014 - 01 Mar 2022
Cited by 8 | Viewed by 3377
Abstract
YAP and TAZ are essential transcriptional co-activators and downstream effectors of the Hippo pathway, regulating cell proliferation, organ growth, and tissue homeostasis. To ask how the Hippo pathway affects mineralized tissue homeostasis in a tissue that is highly reliant on a tight homeostatic [...] Read more.
YAP and TAZ are essential transcriptional co-activators and downstream effectors of the Hippo pathway, regulating cell proliferation, organ growth, and tissue homeostasis. To ask how the Hippo pathway affects mineralized tissue homeostasis in a tissue that is highly reliant on a tight homeostatic control of mineralized deposition and resorption, we determined the effects of YAP/TAZ dysregulation on the periodontal tissues alveolar bone, root cementum, and periodontal ligament. Loss of YAP/TAZ was associated with a reduction of mineralized tissue density in cellular cementum and alveolar bone, a downregulation in collagen I, alkaline phosphatase, and RUNX2 gene expression, an increase in the resorption markers TRAP and cathepsin K, and elevated numbers of TRAP-stained osteoclasts. Cyclic strain applied to periodontal ligament cells resulted in YAP nuclear localization, an effect that was abolished after blocking YAP. The rescue of YAP signaling with the heparan sulfate proteoglycan agrin resulted in a return of the nuclear YAP signal. Illustrating the key role of YAP on mineralization gene expression, the YAP inhibition-related downregulation of mineralization-associated genes was reversed by the extracellular matrix YAP activator agrin. Application of the unopposed mouse molar model to transform the periodontal ligament into an unloaded state and facilitate the distal drift of teeth resulted in an overall increase in mineralization-associated gene expression, an effect that was 10–20% diminished in Wnt1Cre/YAP/TAZ mutant mice. The unloaded state of the unopposed molar model in Wnt1Cre/YAP/TAZ mutant mice also caused a significant three-fold increase in osteoclast numbers, a substantial increase in bone/cementum resorption, pronounced periodontal ligament hyalinization, and thickened periodontal fiber bundles. Together, these data demonstrated that YAP/TAZ signaling is essential for the microarchitectural integrity of the periodontium by regulating mineralization gene expression and preventing excessive resorption during bodily movement of the dentoalveolar complex. Full article
(This article belongs to the Special Issue 2021 Feature Papers by JDB’s Editorial Board Members)
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14 pages, 2346 KiB  
Article
Different Ectopic Hoxa2 Expression Levels in Mouse Cranial Neural Crest Cells Result in Distinct Craniofacial Anomalies and Homeotic Phenotypes
by Taro Kitazawa, Maryline Minoux, Sebastien Ducret and Filippo M. Rijli
J. Dev. Biol. 2022, 10(1), 9; https://doi.org/10.3390/jdb10010009 - 31 Jan 2022
Cited by 9 | Viewed by 3351
Abstract
Providing appropriate positional identity and patterning information to distinct rostrocaudal subpopulations of cranial neural crest cells (CNCCs) is central to vertebrate craniofacial morphogenesis. Hox genes are not expressed in frontonasal and first pharyngeal arch (PA1) CNCCs, whereas a single Hox gene, Hoxa2, [...] Read more.
Providing appropriate positional identity and patterning information to distinct rostrocaudal subpopulations of cranial neural crest cells (CNCCs) is central to vertebrate craniofacial morphogenesis. Hox genes are not expressed in frontonasal and first pharyngeal arch (PA1) CNCCs, whereas a single Hox gene, Hoxa2, is necessary to provide patterning information to second pharyngeal arch (PA2) CNCCs. In frog, chick and mouse embryos, ectopic expression of Hoxa2 in Hox-negative CNCCs induced hypoplastic phenotypes of CNCC derivatives of variable severity, associated or not with homeotic transformation of a subset of PA1 structures into a PA2-like identity. Whether these different morphological outcomes are directly related to distinct Hoxa2 overexpression levels is unknown. To address this issue, we selectively induced Hoxa2 overexpression in mouse CNCCs, using a panel of mouse lines expressing different Hoxa2 ectopic expression levels, including a newly generated Hoxa2 knocked-in mouse line. While ectopic Hoxa2 expression at only 60% of its physiological levels was sufficient for pinna duplication, ectopic Hoxa2 expression at 100% of its normal level was required for complete homeotic repatterning of a subset of PA1 skeletal elements into a duplicated set of PA2-like elements. On the other hand, ectopic Hoxa2 overexpression at non-physiological levels (200% of normal levels) led to an almost complete loss of craniofacial skeletal structures. Moreover, ectopic Hoxa5 overexpression in CNCCs, while also resulting in severe craniofacial defects, did not induce homeotic changes of PA1-derived CNCCs, indicating Hoxa2 specificity in repatterning a subset of Hox-negative CNCCs. These results reconcile some discrepancies in previously published experiments and indicate that distinct subpopulations of CNCCs are differentially sensitive to ectopic levels of Hox expression. Full article
(This article belongs to the Special Issue 2021 Feature Papers by JDB’s Editorial Board Members)
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22 pages, 5884 KiB  
Article
Lysosomal Function Impacts the Skeletal Muscle Extracellular Matrix
by Elizabeth C. Coffey, Mary Astumian, Sarah S. Alrowaished, Claire Schaffer and Clarissa A. Henry
J. Dev. Biol. 2021, 9(4), 52; https://doi.org/10.3390/jdb9040052 - 23 Nov 2021
Cited by 3 | Viewed by 3308
Abstract
Muscle development and homeostasis are critical for normal muscle function. A key aspect of muscle physiology during development, growth, and homeostasis is modulation of protein turnover, the balance between synthesis and degradation of muscle proteins. Protein degradation depends upon lysosomal pH, generated and [...] Read more.
Muscle development and homeostasis are critical for normal muscle function. A key aspect of muscle physiology during development, growth, and homeostasis is modulation of protein turnover, the balance between synthesis and degradation of muscle proteins. Protein degradation depends upon lysosomal pH, generated and maintained by proton pumps. Sphingolipid transporter 1 (spns1), a highly conserved gene encoding a putative late endosome/lysosome carbohydrate/H+ symporter, plays a pivotal role in maintaining optimal lysosomal pH and spns1−/− mutants undergo premature senescence. However, the impact of dysregulated lysosomal pH on muscle development and homeostasis is not well understood. We found that muscle development proceeds normally in spns1−/− mutants prior to the onset of muscle degeneration. Dysregulation of the extracellular matrix (ECM) at the myotendinous junction (MTJ) coincided with the onset of muscle degeneration in spns1−/− mutants. Expression of the ECM proteins laminin 111 and MMP-9 was upregulated. Upregulation of laminin 111 mitigated the severity of muscle degeneration, as inhibition of adhesion to laminin 111 exacerbated muscle degeneration in spns1−/− mutants. MMP-9 upregulation was induced by tnfsf12 signaling, but abrogation of MMP-9 did not impact muscle degeneration in spns1−/− mutants. Taken together, these data indicate that dysregulated lysosomal pH impacts expression of ECM proteins at the myotendinous junction. Full article
(This article belongs to the Special Issue 2021 Feature Papers by JDB’s Editorial Board Members)
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18 pages, 2604 KiB  
Article
Zebrafish Optomotor Response and Morphology Are Altered by Transient, Developmental Exposure to Bisphenol-A
by Mikayla Crowley-Perry, Angelo J. Barberio, Jude Zeino, Erica R. Winston and Victoria P. Connaughton
J. Dev. Biol. 2021, 9(2), 14; https://doi.org/10.3390/jdb9020014 - 02 Apr 2021
Cited by 7 | Viewed by 3288
Abstract
Estrogen-specific endocrine disrupting compounds (EDCs) are potent modulators of neural and visual development and common environmental contaminants. Using zebrafish, we examined the long-term impact of abnormal estrogenic signaling by testing the effects of acute, early exposure to bisphenol-A (BPA), a weak estrogen agonist, [...] Read more.
Estrogen-specific endocrine disrupting compounds (EDCs) are potent modulators of neural and visual development and common environmental contaminants. Using zebrafish, we examined the long-term impact of abnormal estrogenic signaling by testing the effects of acute, early exposure to bisphenol-A (BPA), a weak estrogen agonist, on later visually guided behaviors. Zebrafish aged 24 h postfertilization (hpf), 72 hpf, and 7 days postfertilization (dpf) were exposed to 0.001 μM or 0.1 μM BPA for 24 h, and then allowed to recover for 1 or 2 weeks. Morphology and optomotor responses (OMRs) were assessed after 1 and 2 weeks of recovery for 24 hpf and 72 hpf exposure groups; 7 dpf exposure groups were additionally assessed immediately after exposure. Increased notochord length was seen in 0.001 μM exposed larvae and decreased in 0.1 μM exposed larvae across all age groups. Positive OMR was significantly increased at 1 and 2 weeks post-exposure in larvae exposed to 0.1 μM BPA when they were 72 hpf or 7 dpf, while positive OMR was increased after 2 weeks of recovery in larvae exposed to 0.001 μM BPA at 72 hpf. A time-delayed increase in eye diameter occurred in both BPA treatment groups at 72 hpf exposure; while a transient increase occurred in 7 dpf larvae exposed to 0.1 μM BPA. Overall, short-term developmental exposure to environmentally relevant BPA levels caused concentration- and age-dependent effects on zebrafish visual anatomy and function. Full article
(This article belongs to the Special Issue 2021 Feature Papers by JDB’s Editorial Board Members)
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Review

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13 pages, 432 KiB  
Review
Insights into the Role of Telomeres in Human Embryological Parameters. Opinions Regarding IVF
by George Anifandis, Maria Samara, Mara Simopoulou, Christina I. Messini, Katerina Chatzimeletiou, Eleni Thodou, Alexandros Daponte and Ioannis Georgiou
J. Dev. Biol. 2021, 9(4), 49; https://doi.org/10.3390/jdb9040049 - 13 Nov 2021
Cited by 14 | Viewed by 3336
Abstract
Telomeres promote genome integrity by protecting chromosome ends from the activation of the DNA damage response and protecting chromosomes from the loss of coding sequences due to the end replication problem. Telomere length (TL) is progressively shortened as age progresses, thus resulting in [...] Read more.
Telomeres promote genome integrity by protecting chromosome ends from the activation of the DNA damage response and protecting chromosomes from the loss of coding sequences due to the end replication problem. Telomere length (TL) is progressively shortened as age progresses, thus resulting in cellular senescence. Therefore, TL is in strong adverse linear correlation with aging. Mounting evidence supports the notion that telomeres and male/female infertility are in a close relationship, posing the biology of telomeres as a hot topic in the era of human-assisted reproduction. Specifically, the length of sperm telomeres is gradually increasing as men get older, while the telomere length of the oocytes seems not to follow similar patterns with that of sperm. Nonetheless, the telomere length of the embryos during the cleavage stages seems to have a paternal origin, but the telomere length can be further extended by telomerase activity during the blastocyst stage. The latter has been proposed as a new molecular biomarker with strong predictive value regarding male infertility. As far as the role of telomeres in assisted reproduction, the data is limited but the length of telomeres in both gametes seems to be affected mainly by the cause of infertility rather than the assisted reproductive therapy (ART) procedure itself. The present review aims to shed more light into the role of telomeres in human embryological parameters, including gametes and embryos and also presents opinions regarding the association between telomeres and in vitro fertilization (IVF). Full article
(This article belongs to the Special Issue 2021 Feature Papers by JDB’s Editorial Board Members)
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8 pages, 574 KiB  
Review
In Utero Programming of Testicular Cancer
by David Elad, Ariel J. Jaffa, Dan Grisaru and Ilan Leibovitch
J. Dev. Biol. 2021, 9(3), 35; https://doi.org/10.3390/jdb9030035 - 29 Aug 2021
Cited by 1 | Viewed by 2005
Abstract
It is well established that the intrauterine biological environment plays important roles in fetal development. In this review, we re-visit the hypothesis that testicular germ cell cancer (TGCC), especially in adolescents and young adults, has been programmed in utero. The origin for extreme [...] Read more.
It is well established that the intrauterine biological environment plays important roles in fetal development. In this review, we re-visit the hypothesis that testicular germ cell cancer (TGCC), especially in adolescents and young adults, has been programmed in utero. The origin for extreme in utero environments is mostly maternal driven and may be due to nutritional, physical and psychological stressful conditions that alter the optimal molecular and biophysical in utero environments. Moreover, precursors for TGCC may originate as early as during fertilization or implantation of the blastocyst. Further investigations of human developmental biology, both in vivo and in vitro, are needed in order to establish better understanding of in utero programming of future wellbeing or diseases. Full article
(This article belongs to the Special Issue 2021 Feature Papers by JDB’s Editorial Board Members)
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14 pages, 281 KiB  
Review
Biological and Clinical Significance of Mosaicism in Human Preimplantation Embryos
by Ioanna Bouba, Elissavet Hatzi, Paris Ladias, Prodromos Sakaloglou, Charilaos Kostoulas and Ioannis Georgiou
J. Dev. Biol. 2021, 9(2), 18; https://doi.org/10.3390/jdb9020018 - 07 May 2021
Cited by 6 | Viewed by 3778
Abstract
Applications and indications of assisted reproduction technology are expanding, but every new approach is under scrutiny and thorough consideration. Recently, groups of assisted reproduction experts have presented data that support the clinical use of mosaic preimplantation embryos at the blastocyst stage, previously excluded [...] Read more.
Applications and indications of assisted reproduction technology are expanding, but every new approach is under scrutiny and thorough consideration. Recently, groups of assisted reproduction experts have presented data that support the clinical use of mosaic preimplantation embryos at the blastocyst stage, previously excluded from transfer. In the light of published contemporary studies, with or without clinical outcomes, there is growing evidence that mosaic embryos have the capacity for further in utero development and live birth. Our in-depth discussion will enable readers to better comprehend current developments. This expansion into the spectrum of ART practices requires further evidence and further theoretical documentation, basic research, and ethical support. Therefore, if strict criteria for selecting competent mosaic preimplantation embryos for further transfer, implantation, fetal growth, and healthy birth are applied, fewer embryos will be excluded, and more live births will be achieved. Our review aims to discuss the recent literature on the transfer of mosaic preimplantation embryos. It also highlights controversies as far as the clinical utilization of preimplantation embryos concerns. Finally, it provides the appropriate background to elucidate and highlight cellular and genetic aspects of this novel direction. Full article
(This article belongs to the Special Issue 2021 Feature Papers by JDB’s Editorial Board Members)
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