Analysis of Craniocardiac Malformations in Xenopus using Optical Coherence Tomography

Deniz, Engin; Jonas, Stephan; Hooper, Michael; Griffin, John N.; Choma, Michael A.; Khokha, Mustafa K.

doi:10.1038/srep42506

Cited by 25 publications

(23 citation statements)

References 51 publications

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“…Therefore, any meaningful discussion about skeletal cell evolution needs to include all of the major vertebrate classes (Fig. 3), and despite some recent work, amphibians remain overlooked [3,[26][27][28][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] .…”

Section: Osteoblasts Suppressed Chondrocyte Genes During Evolutionmentioning

confidence: 99%

Evolutionary repression of chondrogenic genes in the vertebrate osteoblast

Nguyen

Eames

2020

The FEBS Journal

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Gene expression in extant animals might reveal how skeletal cells have evolved over the past 500 million years. The cells that make up cartilage (chondrocytes) and bone (osteoblasts) express many of the same genes, but they also have important molecular differences that allow us to distinguish them as separate cell types. For example, traditional studies of later‐diverged vertebrates, such as mouse and chick, defined the genes Col2a1 and sex‐determining region Y‐box 9 as cartilage‐specific. However, recent studies have shown that osteoblasts of earlier‐diverged vertebrates, such as frog, gar, and zebrafish, express these ‘chondrogenic’ markers. In this review, we examine the resulting hypothesis that chondrogenic gene expression became repressed in osteoblasts over evolutionary time. The amphibian is an underexplored skeletal model that is uniquely positioned to address this hypothesis, especially given that it diverged when life transitioned from water to land. Given the relationship between phylogeny and ontogeny, a novel discovery for skeletal cell evolution might bolster our understanding of skeletal cell development.

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Section: Osteoblasts Suppressed Chondrocyte Genes During Evolutionmentioning

confidence: 99%

Evolutionary repression of chondrogenic genes in the vertebrate osteoblast

Nguyen

Eames

2020

The FEBS Journal

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“…Images were taken using a Canon DS126201 camera and Zeiss Discovery V8 SteREO microscope. Optical coherence tomography of the craniofacial cartilages was carried out as previously described (Deniz et al, 2017).…”

Section: Imagingmentioning

confidence: 99%

RPSA, a candidate gene for isolated congenital asplenia, is required for pre-rRNA processing and spleen formation in Xenopus

et al. 2018

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A growing number of tissue-specific inherited disorders are associated with impaired ribosome production, despite the universal requirement for ribosome function. Recently, mutations in RPSA, a protein component of the small ribosomal subunit, were discovered to underlie approximately half of all isolated congenital asplenia cases. However, the mechanisms by which mutations in this ribosome biogenesis factor lead specifically to spleen agenesis remain unknown, in part due to the lack of a suitable animal model for study. Here we reveal that RPSA is required for normal spleen development in the frog, Xenopus tropicalis. Depletion of Rpsa in early embryonic development disrupts pre-rRNA processing and ribosome biogenesis, and impairs expression of the key spleen patterning genes nkx2-5, bapx1 and pod1 in the spleen anlage. Importantly, we also show that whereas injection of human RPSA mRNA can rescue both pre-rRNA processing and spleen patterning, injection of human mRNA bearing a common disease-associated mutation cannot. Together, we present the first animal model of RPSA-mediated asplenia and reveal a crucial requirement for RPSA in pre-rRNA processing and molecular patterning during early Xenopus development.

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“…Xenopus has proven to be an invaluable model for the study of human craniofacial development and disorders [22,[44][45][46][47][48][49][50], given the highly conserved developmental pathways that drive neural crest migration, differentiation, and craniofacial morphogenesis between systems. Nonetheless, there are gross morphological differences that prevent some direct correlations.…”

Section: Whs-associated Gene Depletion In X Laevis Almost Certainly mentioning

confidence: 99%

Wolf-Hirschhorn Syndrome-associated genes are enriched in motile neural crest and affect craniofacial development inXenopus laevis

Mills

Bearce

Cella

et al. 2018

Preprint

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# These authors contributed equally to this work. Keywords craniofacial development | developmental disorders | 4p-| Wolf-Hirschhorn Syndrome | WHSC1 | WHSC2 | LETM1 | TACC3 | neural crest | disease model 1 Abstract 2 Wolf-Hirschhorn Syndrome (WHS) is a human developmental disorder arising from a 3 hemizygous perturbation, typically a microdeletion, on the short arm of chromosome four. In 4 addition to pronounced intellectual disability, seizures, and delayed growth, WHS presents with 5 a characteristic facial dysmorphism and varying prevalence of microcephaly, micrognathia, 6 40 Wolf-Hirschhorn Syndrome (WHS) is a developmental disorder characterized by intellectual 41 disability, delayed pre-and post-natal growth, heart and skeletal defects, and seizures [1-4]. A 42 common clinical marker of WHS is the "Greek Warrior Helmet" appearance; a facial pattern 43 with a characteristic wide and flattened nasal bridge, a high forehead, drastic eyebrow arches and 44 pronounced brow bones, widely spaced eyes (hypertelorism), a short philtrum, and an undersized 45 jaw (micrognathia). The majority of children with the disorder are microcephalic, and have 46 abnormally positioned ears with underdeveloped cartilage. Comorbid midline deficits can occur, 47 including cleft palate and facial asymmetries [1]. 48Craniofacial malformations make up one of the most prevalent forms of congenital defects [5,6], 49 and can significantly complicate palliative care and quality of life [7]. Given the commanding 50 role of cranial neural crest (CNC) cells in virtually all facets of craniofacial patterning, 51 craniofacial abnormalities are typically attributable to aberrant CNC development [6,8]. A 52 striking commonality in the tissues that are impacted by WHS is that a significant number derive 53 from the CNC. Despite this, little is known about how the vast diversity of genetic disruptions 54 that underlie WHS pathology can contribute to craniofacial malformation, and no study has 55 sought to characterize impacts of these genotypes explicitly on CNC behavior. 56WHS is typically caused by small, heterozygous deletions on the short-arm of chromosome 4 57 (4p16.3), which can vary widely in position and length. Initially, deletion of a very small critical 58 region, only partial segments of two genes, was thought to be sufficient for full syndromic 59 presentation [9-13]. These first putative associated genes were appropriately denoted as Wolf- 60Hirschhorn Syndrome Candidates 1 and 2 (WHSC1, WHSC2) [9,11,[14][15][16]. However, children 61 with WHS largely demonstrate 4p disruptions that impact not only this intergenic region between 62 WHSC1 and WHSC2, but instead affect multiple genes both telomeric and centromeric from this 63 locus [17]. Focus was drawn to these broader impacted regions when cases were identified that 64 neglected this first critical region entirely but still showed either full or partial WHS 65 presentation, prompting the expansion of the originally defined critical region to include a more 66 telomeric segment of ...

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Analysis of Craniocardiac Malformations in Xenopus using Optical Coherence Tomography

Cited by 25 publications

References 51 publications

Evolutionary repression of chondrogenic genes in the vertebrate osteoblast

Evolutionary repression of chondrogenic genes in the vertebrate osteoblast

RPSA, a candidate gene for isolated congenital asplenia, is required for pre-rRNA processing and spleen formation in Xenopus

Wolf-Hirschhorn Syndrome-associated genes are enriched in motile neural crest and affect craniofacial development inXenopus laevis

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