Research

18 pages, 2618 KiB

Open AccessArticle

Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease

by Viya B. Fedoseyeva, Ekaterina V. Novosadova, Valentina V. Nenasheva, Lyudmila V. Novosadova, Igor A. Grivennikov and Vyacheslav Z. Tarantul

J. Dev. Biol. 2023, 11(2), 23; https://doi.org/10.3390/jdb11020023 - 25 May 2023

Viewed by 1779

Abstract

Parkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data [...] Read more.

Parkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data of iPSC-derived neural precursor cells (NPCs) and terminally differentiated neurons (TDNs) from healthy donors (HD) and PD patients with mutations in PARK2 published previously. The high level of transcription of HOX family protein-coding genes and lncRNA transcribed from the HOX clusters was revealed in the neural cultures from PD patients, while in HD NPCs and TDNs, the majority of these genes were not expressed or slightly transcribed. The results of this analysis were generally confirmed by qPCR. The HOX paralogs in the 3′ clusters were activated more strongly than the genes of the 5′ cluster. The abnormal activation of the HOX gene program upon neuronal differentiation in the cells of PD patients raises the possibility that the abnormal expression of these key regulators of neuronal development impacts PD pathology. Further research is needed to investigate this hypothesis. Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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23 pages, 4437 KiB

Open AccessArticle

The Development of the Chimaeroid Pelvic Skeleton and the Evolution of Chondrichthyan Pelvic Fins

by Jacob B. Pears, Carley Tillett, Rui Tahara, Hans C. E. Larsson, Kate Trinajstic and Catherine A. Boisvert

J. Dev. Biol. 2022, 10(4), 53; https://doi.org/10.3390/jdb10040053 - 12 Dec 2022

Viewed by 3719

Abstract

Pelvic girdles, fins and claspers are evolutionary novelties first recorded in jawed vertebrates. Over the course of the evolution of chondrichthyans (cartilaginous fish) two trends in the morphology of the pelvic skeleton have been suggested to have occurred. These evolutionary shifts involved both [...] Read more.

Pelvic girdles, fins and claspers are evolutionary novelties first recorded in jawed vertebrates. Over the course of the evolution of chondrichthyans (cartilaginous fish) two trends in the morphology of the pelvic skeleton have been suggested to have occurred. These evolutionary shifts involved both an enlargement of the metapterygium (basipterygium) and a transition of fin radial articulation from the pelvic girdle to the metapterygium. To determine how these changes in morphology have occurred it is essential to understand the development of extant taxa as this can indicate potential developmental mechanisms that may have been responsible for these changes. The study of the morphology of the appendicular skeleton across development in chondrichthyans is almost entirely restricted to the historical literature with little contemporary research. Here, we have examined the morphology and development of the pelvic skeleton of a holocephalan chondrichthyan, the elephant shark (Callorhinchus milii), through a combination of dissections, histology, and nanoCT imaging and redescribed the pelvic skeleton of Cladoselache kepleri (NHMUK PV P 9269), a stem holocephalan. To put our findings in their evolutionary context we compare them with the fossil record of chondrichthyans and the literature on pelvic development in elasmobranchs from the late 19th century. Our findings demonstrate that the pelvic skeleton of C. milii initially forms as a single mesenchymal condensation, consisting of the pelvic girdle and a series of fin rays, which fuse to form the basipterygium. The girdle and fin skeleton subsequently segment into distinct components whilst chondrifying. This confirms descriptions of the early pelvic development in Scyliorhinid sharks from the historical literature and suggests that chimaeras and elasmobranchs share common developmental patterns in their pelvic anatomy. Alterations in the location and degree of radial fusion during early development may be the mechanism responsible for changes in pelvic fin morphology over the course of the evolution of both elasmobranchs and holocephalans, which appears to be an example of parallel evolution. Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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13 pages, 3382 KiB

Open AccessArticle

The Shape of the Jaw—Zebrafish Col11a1a Regulates Meckel’s Cartilage Morphogenesis and Mineralization

by Jonathon C. Reeck and Julia Thom Oxford

J. Dev. Biol. 2022, 10(4), 40; https://doi.org/10.3390/jdb10040040 - 22 Sep 2022

Cited by 3 | Viewed by 2345

Abstract

The expression of the col11a1a gene is essential for normal skeletal development, affecting both cartilage and bone. Loss of function mutations have been shown to cause abnormalities in the growth plate of long bones, as well as in craniofacial development. However, the specific [...] Read more.

The expression of the col11a1a gene is essential for normal skeletal development, affecting both cartilage and bone. Loss of function mutations have been shown to cause abnormalities in the growth plate of long bones, as well as in craniofacial development. However, the specific effects on Meckel’s cartilage have not been well studied. To further understand the effect of col11a1a gene function, we analyzed the developing jaw in zebrafish using gene knockdown by the injection of an antisense morpholino oligonucleotide using transgenic Tg(sp7:EGFP) and Tg(Fli1a:EGFP) EGFP reporter fish, as well as wildtype AB zebrafish. Our results demonstrate that zebrafish col11a1a knockdown impairs the cellular organization of Meckel’s cartilage in the developing jaw and alters the bone formation that occurs adjacent to the Meckel’s cartilage. These results suggest roles for Col11a1a protein in cartilage intermediates of bone development, the subsequent mineralization of the bony collar of long bones, and that which occurs adjacent to Meckel’s cartilage in the developing jaw. Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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21 pages, 3843 KiB

Open AccessFeature PaperArticle

Pax3 Hypomorphs Reveal Hidden Pax7 Functional Genetic Compensation in Utero

by Hong-Ming Zhou and Simon J. Conway

J. Dev. Biol. 2022, 10(2), 19; https://doi.org/10.3390/jdb10020019 - 17 May 2022

Cited by 1 | Viewed by 2836

Abstract

Pax3 and Pax7 transcription factors are paralogs within the Pax gene family that that are expressed in early embryos in partially overlapping expression domains and have distinct functions. Significantly, mammalian development is largely unaffected by Pax7 systemic deletion but systemic Pax3 deletion results [...] Read more.

Pax3 and Pax7 transcription factors are paralogs within the Pax gene family that that are expressed in early embryos in partially overlapping expression domains and have distinct functions. Significantly, mammalian development is largely unaffected by Pax7 systemic deletion but systemic Pax3 deletion results in defects in neural tube closure, neural crest emigration, cardiac outflow tract septation, muscle hypoplasia and in utero lethality by E14. However, we previously demonstrated that Pax3 hypomorphs expressing only 20% functional Pax3 protein levels exhibit normal neural tube and heart development, but myogenesis is selectively impaired. To determine why only some Pax3-expressing cell lineages are affected and to further titrate Pax3 threshold levels required for neural tube and heart development, we generated hypomorphs containing both a hypomorphic and a null Pax3 allele. This resulted in mutants only expressing 10% functional Pax3 protein with exacerbated neural tube, neural crest and muscle defects, but still a normal heart. To examine why the cardiac neural crest appears resistant to very low Pax3 levels, we examined its paralog Pax7. Significantly, Pax7 expression is both ectopically expressed in Pax3-expressing dorsal neural tube cells and is also upregulated in the Pax3-expressing lineages. To test whether this compensatory Pax7 expression is functional, we deleted Pax7 both systemically and lineage-specifically in hypomorphs expressing only 10% Pax3. Removal of one Pax7 allele resulted in partial outflow tract defects, and complete loss of Pax7 resulted in full penetrance outflow tract defects and in utero lethality. Moreover, combinatorial loss of Pax3 and Pax7 resulted in severe craniofacial defects and a total block of neural crest cell emigration from the neural tube. Pax7^Cre lineage mapping revealed ectopic labeling of Pax3-derived neural crest tissues and within the outflow tract of the heart, experimentally confirming the observation of ectopic activation of Pax7 in 10% Pax3 hypomorphs. Finally, genetic cell ablation of Pax7^Cr^e-marked cells is sufficient to cause outflow tract defects in hypomorphs expressing only 10% Pax3, confirming that ectopic and induced Pax7 can play an overlapping functional genetic compensational role in both cardiac neural crest lineage and during craniofacial development, which is normally masked by the dominant role of Pax3. Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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Review

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22 pages, 1175 KiB

Open AccessFeature PaperReview

The Lost and Found: Unraveling the Functions of Orphan Genes

by Ali Zeeshan Fakhar, Jinbao Liu, Karolina M. Pajerowska-Mukhtar and M. Shahid Mukhtar

J. Dev. Biol. 2023, 11(2), 27; https://doi.org/10.3390/jdb11020027 - 13 Jun 2023

Cited by 2 | Viewed by 3379

Abstract

Orphan Genes (OGs) are a mysterious class of genes that have recently gained significant attention. Despite lacking a clear evolutionary history, they are found in nearly all living organisms, from bacteria to humans, and they play important roles in diverse biological processes. The [...] Read more.

Orphan Genes (OGs) are a mysterious class of genes that have recently gained significant attention. Despite lacking a clear evolutionary history, they are found in nearly all living organisms, from bacteria to humans, and they play important roles in diverse biological processes. The discovery of OGs was first made through comparative genomics followed by the identification of unique genes across different species. OGs tend to be more prevalent in species with larger genomes, such as plants and animals, and their evolutionary origins remain unclear but potentially arise from gene duplication, horizontal gene transfer (HGT), or de novo origination. Although their precise function is not well understood, OGs have been implicated in crucial biological processes such as development, metabolism, and stress responses. To better understand their significance, researchers are using a variety of approaches, including transcriptomics, functional genomics, and molecular biology. This review offers a comprehensive overview of the current knowledge of OGs in all domains of life, highlighting the possible role of dark transcriptomics in their evolution. More research is needed to fully comprehend the role of OGs in biology and their impact on various biological processes. Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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26 pages, 3394 KiB

Open AccessReview

Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish

by Bridgette E. Drummond, Wesley S. Ercanbrack and Rebecca A. Wingert

J. Dev. Biol. 2023, 11(1), 9; https://doi.org/10.3390/jdb11010009 - 20 Feb 2023

Cited by 5 | Viewed by 4069

Abstract

Podocytes are exquisitely fashioned kidney cells that serve an essential role in the process of blood filtration. Congenital malformation or damage to podocytes has dire consequences and initiates a cascade of pathological changes leading to renal disease states known as podocytopathies. In addition, [...] Read more.

Podocytes are exquisitely fashioned kidney cells that serve an essential role in the process of blood filtration. Congenital malformation or damage to podocytes has dire consequences and initiates a cascade of pathological changes leading to renal disease states known as podocytopathies. In addition, animal models have been integral to discovering the molecular pathways that direct the development of podocytes. In this review, we explore how researchers have used the zebrafish to illuminate new insights about the processes of podocyte ontogeny, model podocytopathies, and create opportunities to discover future therapies. Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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22 pages, 6666 KiB

Open AccessReview

Organophosphate Insecticide Toxicity in Neural Development, Cognition, Behaviour and Degeneration: Insights from Zebrafish

by Jeremy Neylon, Jarrad N. Fuller, Chris van der Poel, Jarrod E. Church and Sebastian Dworkin

J. Dev. Biol. 2022, 10(4), 49; https://doi.org/10.3390/jdb10040049 - 21 Nov 2022

Cited by 9 | Viewed by 5584

Abstract

Organophosphate (OP) insecticides are used to eliminate agricultural threats posed by insects, through inhibition of the neurotransmitter acetylcholinesterase (AChE). These potent neurotoxins are extremely efficacious in insect elimination, and as such, are the preferred agricultural insecticides worldwide. Despite their efficacy, however, estimates indicate [...] Read more.

Organophosphate (OP) insecticides are used to eliminate agricultural threats posed by insects, through inhibition of the neurotransmitter acetylcholinesterase (AChE). These potent neurotoxins are extremely efficacious in insect elimination, and as such, are the preferred agricultural insecticides worldwide. Despite their efficacy, however, estimates indicate that only 0.1% of organophosphates reach their desired target. Moreover, multiple studies have shown that OP exposure in both humans and animals can lead to aberrations in embryonic development, defects in childhood neurocognition, and substantial contribution to neurodegenerative diseases such as Alzheimer’s and Motor Neurone Disease. Here, we review the current state of knowledge pertaining to organophosphate exposure on both embryonic development and/or subsequent neurological consequences on behaviour, paying particular attention to data gleaned using an excellent animal model, the zebrafish (Danio rerio). Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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15 pages, 1371 KiB

Open AccessFeature PaperReview

Cleft Palate in Apert Syndrome

by Delayna Willie, Greg Holmes, Ethylin Wang Jabs and Meng Wu

J. Dev. Biol. 2022, 10(3), 33; https://doi.org/10.3390/jdb10030033 - 11 Aug 2022

Cited by 5 | Viewed by 4674

Abstract

Apert syndrome is a rare genetic disorder characterized by craniosynostosis, midface retrusion, and limb anomalies. Cleft palate occurs in a subset of Apert syndrome patients. Although the genetic causes underlying Apert syndrome have been identified, the downstream signaling pathways and cellular mechanisms responsible [...] Read more.

Apert syndrome is a rare genetic disorder characterized by craniosynostosis, midface retrusion, and limb anomalies. Cleft palate occurs in a subset of Apert syndrome patients. Although the genetic causes underlying Apert syndrome have been identified, the downstream signaling pathways and cellular mechanisms responsible for cleft palate are still elusive. To find clues for the pathogenic mechanisms of palatal defects in Apert syndrome, we review the clinical characteristics of the palate in cases of Apert syndrome, the palatal phenotypes in mouse models, and the potential signaling mechanisms involved in palatal defects. In Apert syndrome patients, cleft of the soft palate is more frequent than of the hard palate. The length of the hard palate is decreased. Cleft palate is associated most commonly with the S252W variant of FGFR2. In addition to cleft palate, high-arched palate, lateral palatal swelling, or bifid uvula are common in Apert syndrome patients. Mouse models of Apert syndrome display palatal defects, providing valuable tools to understand the underlying mechanisms. The mutations in FGFR2 causing Apert syndrome may change a signaling network in epithelial–mesenchymal interactions during palatogenesis. Understanding the pathogenic mechanisms of palatal defects in Apert syndrome may shed light on potential novel therapeutic solutions. Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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21 pages, 1644 KiB

Open AccessReview

The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review

by Daniel Halloran, Venu Pandit and Anja Nohe

J. Dev. Biol. 2022, 10(3), 31; https://doi.org/10.3390/jdb10030031 - 27 Jul 2022

Cited by 6 | Viewed by 3462

Abstract

Protein kinase CK2 (CK2) is a ubiquitous holoenzyme involved in a wide array of developmental processes. The involvement of CK2 in events such as neurogenesis, cardiogenesis, skeletogenesis, and spermatogenesis is essential for the viability of almost all organisms, and its role has been [...] Read more.

Protein kinase CK2 (CK2) is a ubiquitous holoenzyme involved in a wide array of developmental processes. The involvement of CK2 in events such as neurogenesis, cardiogenesis, skeletogenesis, and spermatogenesis is essential for the viability of almost all organisms, and its role has been conserved throughout evolution. Further into adulthood, CK2 continues to function as a key regulator of pathways affecting crucial processes such as osteogenesis, adipogenesis, chondrogenesis, neuron differentiation, and the immune response. Due to its vast role in a multitude of pathways, aberrant functioning of this kinase leads to embryonic lethality and numerous diseases and disorders, including cancer and neurological disorders. As a result, CK2 is a popular target for interventions aiming to treat the aforementioned diseases. Specifically, two CK2 inhibitors, namely CX-4945 and CIBG-300, are in the early stages of clinical testing and exhibit promise for treating cancer and other disorders. Further, other researchers around the world are focusing on CK2 to treat bone disorders. This review summarizes the current understanding of CK2 in development, the structure of CK2, the targets and signaling pathways of CK2, the implication of CK2 in disease progression, and the recent therapeutics developed to inhibit the dysregulation of CK2 function in various diseases. Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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Other

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9 pages, 2636 KiB

Open AccessBrief Report

Patterning of the Vertebrate Head in Time and Space by BMP Signaling

by Kongju Zhu, Herman P. Spaink and Antony J. Durston

J. Dev. Biol. 2023, 11(3), 31; https://doi.org/10.3390/jdb11030031 - 03 Jul 2023

Cited by 1 | Viewed by 1364

Abstract

How head patterning is regulated in vertebrates is yet to be understood. In this study, we show that frog embryos injected with Noggin at different blastula and gastrula stages had their head development sequentially arrested at different positions. When timed BMP inhibition was [...] Read more.

How head patterning is regulated in vertebrates is yet to be understood. In this study, we show that frog embryos injected with Noggin at different blastula and gastrula stages had their head development sequentially arrested at different positions. When timed BMP inhibition was applied to BMP-overexpressing embryos, the expression of five genes: xcg-1 (a marker of the cement gland, which is the front-most structure in the frog embryo), six3 (a forebrain marker), otx2 (a forebrain and mid-brain marker), gbx2 (an anterior hindbrain marker), and hoxd1 (a posterior hindbrain marker) were sequentially fixed. These results suggest that the vertebrate head is patterned from anterior to posterior in a progressive fashion and may involve timed actions of the BMP signaling. Full article

(This article belongs to the Special Issue 2022 Feature Papers by JDB’s Editorial Board Members)

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