Journal of Developmental Biology

12 pages, 5720 KiB

Open AccessArticle

Cracd Marks the First Wave of Meiosis during Spermatogenesis and Is Mis-Expressed in Azoospermia Mice

by Paige L. Snider, Olga Simmons and Simon J. Conway

J. Dev. Biol. 2020, 8(3), 21; https://doi.org/10.3390/jdb8030021 - 18 Sep 2020

Cited by 3 | Viewed by 2786

Testicular development starts in utero and maturation continues postnatally, requiring a cascade of gene activation and differentiation into different cell types, with each cell type having its own specific function. As we had previously reported that the Capping protein inhibiting regulator of actin [...] Read more.

Testicular development starts in utero and maturation continues postnatally, requiring a cascade of gene activation and differentiation into different cell types, with each cell type having its own specific function. As we had previously reported that the Capping protein inhibiting regulator of actin (Cracd) gene was expressed in the adult mouse testis, herein we examine when and where the β-catenin associated Cracd is initially expressed during postnatal testis development. Significantly, Cracd mRNA is present in both the immature postnatal and adult testis in round spermatid cells, with highest level of expression occurring during the first wave of meiosis and spermatogenesis. In the juvenile testes, Cracd is initially expressed within the innermost region but as maturation occurs, Cracd mRNA switches to a more peripheral location. Thereafter, Cracd is downregulated to maintenance levels in the haploid male germ cell lineage. As Cracd mRNA was expressed within developing round spermatids, we tested its effectiveness as a biomarker of non-obstructive azoospermia using transgenic knockout mice models. Meaningfully, Cracd expression was absent in Deleted in azoospermia like (Dazl) null testis, which exhibit a dramatic germ cell loss. Moreover, Cracd was abnormally regulated and ectopically mis-expressed in Polypyrimidine tract binding protein-2 (Ptbp2) conditional germ cell restricted knockout testis, which exhibit a block during spermatid differentiation and a reduction in the number of late stage spermatocytes coincident with reduced β-catenin expression. Combined, these data suggest that Cracd is a useful first wave of spermatogenesis biomarker of azoospermia phenotypes, even prior to an overt phenotype being evident. Full article

(This article belongs to the Special Issue 2020 Feature Papers by JDB’s Editorial Board Members)

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18 pages, 36980 KiB

Open AccessArticle

Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis

by Seungshin Ha, Prem P. Tripathi, Ray A. Daza, Robert F. Hevner and David R. Beier

J. Dev. Biol. 2020, 8(3), 20; https://doi.org/10.3390/jdb8030020 - 18 Sep 2020

Cited by 5 | Viewed by 3351

Abstract

We have previously described hypomorphic reelin (Reln) mutant mice, Reln^CTRdel, in which the morphology of the dentate gyrus is distinct from that seen in reeler mice. In the Reln^CTRdel mutant, the infrapyramidal blade of the dentate gyrus fails [...] Read more.

We have previously described hypomorphic reelin (Reln) mutant mice, Reln^CTRdel, in which the morphology of the dentate gyrus is distinct from that seen in reeler mice. In the Reln^CTRdel mutant, the infrapyramidal blade of the dentate gyrus fails to extend, while the suprapyramidal blade forms with a relatively compact granule neuron layer. Underlying this defect, we now report several developmental anomalies in the Reln^CTRdel dentate gyrus. Most strikingly, the distribution of Cajal-Retzius cells was aberrant; Cajal-Retzius neurons were increased in the suprapyramidal blade, but were greatly reduced along the subpial surface of the prospective infrapyramidal blade. We also observed multiple abnormalities of the fimbriodentate junction. Firstly, progenitor cells were distributed abnormally; the “neurogenic cluster” at the fimbriodentate junction was absent, lacking the normal accumulation of Tbr2-positive intermediate progenitors. However, the number of dividing cells in the dentate gyrus was not generally decreased. Secondly, a defect of secondary glial scaffold formation, limited to the infrapyramidal blade, was observed. The densely radiating glial fibers characteristic of the normal fimbriodentate junction were absent in mutants. These fibers might be required for migration of progenitors, which may account for the failure of neurogenic cluster formation. These findings suggest the importance of the secondary scaffold and neurogenic cluster of the fimbriodentate junction in morphogenesis of the mammalian dentate gyrus. Our study provides direct genetic evidence showing that normal RELN function is required for Cajal-Retzius cell positioning in the dentate gyrus, and for formation of the fimbriodentate junction to promote infrapyramidal blade extension. Full article

(This article belongs to the Special Issue 2020 Feature Papers by JDB’s Editorial Board Members)

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30 pages, 1951 KiB

Open AccessFeature PaperReview

Bone Morphogenetic Protein-2 in Development and Bone Homeostasis

by Daniel Halloran, Hilary W. Durbano and Anja Nohe

J. Dev. Biol. 2020, 8(3), 19; https://doi.org/10.3390/jdb8030019 - 13 Sep 2020

Cited by 167 | Viewed by 15775

Abstract

Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the Transforming Growth Factor-Beta (TGF-β) superfamily. These proteins are essential to many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Specifically, within the BMP family, Bone Morphogenetic Protein-2 (BMP-2) was the first BMP to [...] Read more.

Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the Transforming Growth Factor-Beta (TGF-β) superfamily. These proteins are essential to many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Specifically, within the BMP family, Bone Morphogenetic Protein-2 (BMP-2) was the first BMP to be characterized and has been well-studied. BMP-2 has important roles during embryonic development, as well as bone remodeling and homeostasis in adulthood. Some of its specific functions include digit formation and activating osteogenic genes, such as Runt-Related Transcription Factor 2 (RUNX2). Because of its diverse functions and osteogenic potential, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery, tibial shaft repair, and maxillary sinus reconstructive surgery. However, shortly after initial injections of rhBMP-2, several adverse complications were reported, and alternative therapeutics have been developed to limit these side-effects. As the clinical application of BMP-2 is largely implicated in bone, we focus primarily on its role in bone. However, we also describe briefly the role of BMP-2 in development. We then focus on the structure of BMP-2, its activation and regulation signaling pathways, BMP-2 clinical applications, and limitations of using BMP-2 as a therapeutic. Further, this review explores other potential treatments that may be useful in treating bone disorders. Full article

(This article belongs to the Special Issue Feature Papers in Journal of Developmental Biology)

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27 pages, 1725 KiB

Open AccessReview

Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis

by Erica M. Siismets and Nan E. Hatch

J. Dev. Biol. 2020, 8(3), 18; https://doi.org/10.3390/jdb8030018 - 9 Sep 2020

Cited by 32 | Viewed by 10519

Abstract

Craniofacial anomalies are among the most common of birth defects. The pathogenesis of craniofacial anomalies frequently involves defects in the migration, proliferation, and fate of neural crest cells destined for the craniofacial skeleton. Genetic mutations causing deficient cranial neural crest migration and proliferation [...] Read more.

Craniofacial anomalies are among the most common of birth defects. The pathogenesis of craniofacial anomalies frequently involves defects in the migration, proliferation, and fate of neural crest cells destined for the craniofacial skeleton. Genetic mutations causing deficient cranial neural crest migration and proliferation can result in Treacher Collins syndrome, Pierre Robin sequence, and cleft palate. Defects in post-migratory neural crest cells can result in pre- or post-ossification defects in the developing craniofacial skeleton and craniosynostosis (premature fusion of cranial bones/cranial sutures). The coronal suture is the most frequently fused suture in craniosynostosis syndromes. It exists as a biological boundary between the neural crest-derived frontal bone and paraxial mesoderm-derived parietal bone. The objective of this review is to frame our current understanding of neural crest cells in craniofacial development, craniofacial anomalies, and the pathogenesis of coronal craniosynostosis. We will also discuss novel approaches for advancing our knowledge and developing prevention and/or treatment strategies for craniofacial tissue regeneration and craniosynostosis. Full article

(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)

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Graphical abstract

18 pages, 1660 KiB

Open AccessReview

A Series of Tubes: The C. elegans Excretory Canal Cell as a Model for Tubule Development

by Matthew Buechner, Zhe Yang and Hikmat Al-Hashimi

J. Dev. Biol. 2020, 8(3), 17; https://doi.org/10.3390/jdb8030017 - 7 Sep 2020

Cited by 4 | Viewed by 7616

Abstract

Formation and regulation of properly sized epithelial tubes is essential for multicellular life. The excretory canal cell of C. elegans provides a powerful model for investigating the integration of the cytoskeleton, intracellular transport, and organismal physiology to regulate the developmental processes of tube [...] Read more.

Formation and regulation of properly sized epithelial tubes is essential for multicellular life. The excretory canal cell of C. elegans provides a powerful model for investigating the integration of the cytoskeleton, intracellular transport, and organismal physiology to regulate the developmental processes of tube extension, lumen formation, and lumen diameter regulation in a narrow single cell. Multiple studies have provided new understanding of actin and intermediate filament cytoskeletal elements, vesicle transport, and the role of vacuolar ATPase in determining tube size. Most of the genes discovered have clear homologues in humans, with implications for understanding these processes in mammalian tissues such as Schwann cells, renal tubules, and brain vasculature. The results of several new genetic screens are described that provide a host of new targets for future studies in this informative structure. Full article

(This article belongs to the Special Issue Caenorhabditis elegans - A Developmental Genetic Model System)

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16 pages, 2896 KiB

Open AccessFeature PaperArticle

Col11a1a Expression Is Required for Zebrafish Development

by Makenna J. Hardy, Jonathon C. Reeck, Ming Fang, Jason S. Adams and Julia Thom Oxford

J. Dev. Biol. 2020, 8(3), 16; https://doi.org/10.3390/jdb8030016 - 28 Aug 2020

Cited by 3 | Viewed by 3708

Abstract

The autosomal dominant chondrodystrophies, the Stickler type 2 and Marshall syndromes, are characterized by facial abnormalities, vision deficits, hearing loss, and articular joint issues resulting from mutations in COL11A1. Zebrafish carry two copies of the Col11a1 gene, designated Col11a1a and Col11a1b. [...] Read more.

The autosomal dominant chondrodystrophies, the Stickler type 2 and Marshall syndromes, are characterized by facial abnormalities, vision deficits, hearing loss, and articular joint issues resulting from mutations in COL11A1. Zebrafish carry two copies of the Col11a1 gene, designated Col11a1a and Col11a1b. Col11a1a is located on zebrafish chromosome 24 and Col11a1b is located on zebrafish chromosome 2. Expression patterns are distinct for Col11a1a and Col11a1b and Col11a1a is most similar to COL11A1 that is responsible for human autosomal chondrodystrophies and the gene responsible for changes in the chondrodystrophic mouse model cho/cho. We investigated the function of Col11a1a in craniofacial and axial skeletal development in zebrafish using a knockdown approach. Knockdown revealed abnormalities in Meckel’s cartilage, the otoliths, and overall body length. Similar phenotypes were observed using a CRISPR/Cas9 gene-editing approach, although the CRISPR/Cas9 effect was more severe compared to the transient effect of the antisense morpholino oligonucleotide treatment. The results of this study provide evidence that the zebrafish gene for Col11a1a is required for normal development and has similar functions to the mammalian COL11A1 gene. Due to its transparency, external fertilization, the Col11a1a knockdown, and knockout zebrafish model systems can, therefore, contribute to filling the gap in knowledge about early events during vertebrate skeletal development that are not as tenable in mammalian model systems and help us understand Col11a1-related early developmental events. Full article

(This article belongs to the Special Issue Advances in Development: Focus on Rare Congenital Diseases)

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2 pages, 154 KiB

Open AccessEditorial

Special Issue “Zebrafish-A Model System for Developmental Biology Study”

by Lisa Maves

J. Dev. Biol. 2020, 8(3), 15; https://doi.org/10.3390/jdb8030015 - 4 Aug 2020

Cited by 2 | Viewed by 2505

Abstract

For this Special Issue “Zebrafish-A Model System for Developmental Biology Study,” we present a collection of studies, including original research papers and review articles, that focus on advances in developmental biology research and that take advantage of the zebrafish model organism [...] Full article

(This article belongs to the Special Issue Zebrafish - A Model System for Developmental Biology Study)

18 pages, 1202 KiB

Open AccessFeature PaperReview

Recent Advances in the Genetic, Anatomical, and Environmental Regulation of the C. elegans Germ Line Progenitor Zone

by Kacy Gordon

J. Dev. Biol. 2020, 8(3), 14; https://doi.org/10.3390/jdb8030014 - 22 Jul 2020

Cited by 5 | Viewed by 5212

Abstract

The C. elegans germ line and its gonadal support cells are well studied from a developmental genetics standpoint and have revealed many foundational principles of stem cell niche biology. Among these are the observations that a niche-like cell supports a self-renewing stem cell [...] Read more.

The C. elegans germ line and its gonadal support cells are well studied from a developmental genetics standpoint and have revealed many foundational principles of stem cell niche biology. Among these are the observations that a niche-like cell supports a self-renewing stem cell population with multipotential, differentiating daughter cells. While genetic features that distinguish stem-like cells from their differentiating progeny have been defined, the mechanisms that structure these populations in the germ line have yet to be explained. The spatial restriction of Notch activation has emerged as an important genetic principle acting in the distal germ line. Synthesizing recent findings, I present a model in which the germ stem cell population of the C. elegans adult hermaphrodite can be recognized as two distinct anatomical and genetic populations. This review describes the recent progress that has been made in characterizing the undifferentiated germ cells and gonad anatomy, and presents open questions in the field and new directions for research to pursue. Full article

(This article belongs to the Special Issue Caenorhabditis elegans - A Developmental Genetic Model System)

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16 pages, 3292 KiB

Open AccessArticle

Cerebellar Morphology and Behavioral Profiles in Mice Lacking Heparan Sulfate Ndst Gene Function

by Lars Lewejohann, Srinivas R. Pallerla, Rebecca S. Schreiber, Joanna Gerula and Kay Grobe

J. Dev. Biol. 2020, 8(3), 13; https://doi.org/10.3390/jdb8030013 - 11 Jul 2020

Cited by 4 | Viewed by 3532

Abstract

Disruption of the Heparan sulfate (HS)-biosynthetic gene N-acetylglucosamine N-Deacetylase/N-sulfotransferase 1 (Ndst1) during nervous system development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. However, the role of Ndst function in adult [...] Read more.

Disruption of the Heparan sulfate (HS)-biosynthetic gene N-acetylglucosamine N-Deacetylase/N-sulfotransferase 1 (Ndst1) during nervous system development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. However, the role of Ndst function in adult brain physiology is less explored. Therefore, we generated mice bearing a Purkinje-cell-specific deletion in Ndst1 gene function by using Cre/loxP technology under the control of the Purkinje cell protein 2 (Pcp2/L7) promotor, which results in HS undersulfation. We observed that mutant mice did not show overt changes in the density or organization of Purkinje cells in the adult cerebellum, and behavioral tests also demonstrated normal cerebellar function. This suggested that postnatal Purkinje cell development and homeostasis are independent of Ndst1 function, or that impaired HS sulfation upon deletion of Ndst1 function may be compensated for by other Purkinje cell-expressed Ndst isoforms. To test the latter possibility, we additionally deleted the second Purkinje-cell expressed Ndst family member, Ndst2. This selectively abolished reproductive capacity of compound mutant female, but not male, mice, suggesting that ovulation, gestation, or female reproductive behavior specifically depends on Ndst-dependent HS sulfation in cells types that express Cre under Pcp2/L7 promotor control. Full article

(This article belongs to the Special Issue Feature Papers in Journal of Developmental Biology)

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23 pages, 4592 KiB

Open AccessArticle

A Synthetic Peptide, CK2.3, Inhibits RANKL-Induced Osteoclastogenesis through BMPRIa and ERK Signaling Pathway

by John Nguyen, Semaj Kelly, Ryan Wood, Brian Heubel and Anja Nohe

J. Dev. Biol. 2020, 8(3), 12; https://doi.org/10.3390/jdb8030012 - 9 Jul 2020

Cited by 7 | Viewed by 3868

Abstract

The skeletal system plays an important role in the development and maturation process. Through the bone remodeling process, 10% of the skeletal system is renewed every year. Osteoblasts and osteoclasts are two major bone cells that are involved in the development of the [...] Read more.

The skeletal system plays an important role in the development and maturation process. Through the bone remodeling process, 10% of the skeletal system is renewed every year. Osteoblasts and osteoclasts are two major bone cells that are involved in the development of the skeletal system, and their activity is kept in balance. An imbalance between their activities can lead to diseases such as osteoporosis that are characterized by significant bone loss due to the overactivity of bone-resorbing osteoclasts. Our laboratory has developed a novel peptide, CK2.3, which works as both an anabolic and anti-resorptive agent to induce bone formation and prevent bone loss. We previously reported that CK2.3 mediated mineralization and osteoblast development through the SMAD, ERK, and AKT signaling pathways. In this study, we demonstrated the mechanism by which CK2.3 inhibits osteoclast development. We showed that the inhibition of MEK by the U0126 inhibitor rescued the osteoclast development of RAW264.7 induced by RANKL in a co-culture system with CK2.3. We observed that CK2.3 induced ERK activation and BMPRIa expression on Day 1 after stimulation with CK2.3. While CK2.3 was previously reported to induce the SMAD signaling pathway in osteoblast development, we did not observe any changes in SMAD activation in osteoclast development with CK2.3 stimulation. Understanding the mechanism by which CK2.3 inhibits osteoclast development will allow CK2.3 to be developed as a new treatment for osteoporosis. Full article

(This article belongs to the Special Issue Feature Papers in Journal of Developmental Biology)

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