p.E95K mutation in Indian hedgehog causing brachydactyly type A1 impairs IHH/Gli1 downstream transcriptional regulation

Shen, Lu; Ma, Gang; Shi, Ye; Ruan, Yunfeng; Yang, Xuhan; Wu, Xi; Xiong, Yüting; Wan, Chunling; Yang, Chao; Xiong, Likuan; Gong, Xiaohua; Qin, Shengying

doi:10.1186/s12863-018-0697-5

Cited by 7 publications

(4 citation statements)

References 53 publications

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“…6 A ) . HSD17B8 and LRP2 , and also other genes related to lipid transport (e.g., nrf-6 ), are involved in fatty acid biosynthesis during oocyte maturation of the crab Eriocheir sinensis ( Chen et al. 2019 ).…”

Section: Resultsmentioning

confidence: 99%

The Molecular Machinery of Gametogenesis inGeodiaDemosponges (Porifera): Evolutionary Origins of a Conserved Toolkit across Animals

Koutsouveli

Cárdenas

Santodomingo

et al. 2020

Molecular Biology and Evolution

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All animals are capable of undergoing gametogenesis. The ability of forming haploid cells from diploid cells through meiosis and recombination appeared early in eukaryotes, while further gamete differentiation is mostly a metazoan signature. Morphologically, the gametogenic process presents many similarities across animal taxa, but little is known about its conservation at the molecular level. Porifera are the earliest divergent animals and therefore are an ideal phylum to understand evolution of the gametogenic toolkits. While sponge gametogenesis is well known at the histological level, the molecular toolkits for gamete production are largely unknown. Our goal was to identify the genes and their expression levels which regulate oogenesis and spermatogenesis in five gonochoristic and oviparous species of the genus Geodia, using both RNAseq and proteomic analyses. In the early stages of both female and male gametogenesis, genes involved in germ cell fate and cell-renewal were upregulated. Then, molecular signals involved in retinoic acid pathway could trigger the meiotic processes. During later stages of oogenesis, female sponges expressed genes involved in cell growth, vitellogenesis and extracellular matrix reassembly, which are conserved elements of oocyte maturation in Metazoa. Likewise, in spermatogenesis, genes regulating the whole meiotic cycle, chromatin compaction, and flagellum axoneme formation that are common across Metazoa, were overexpressed in our sponges. Finally, molecular signals possibly related to sperm capacitation were identified during late stages of spermatogenesis for the first time in Porifera. In conclusion, the activated molecular toolkit during gametogenesis in sponges was remarkably similar to that deployed during gametogenesis in vertebrates.

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Section: Resultsmentioning

confidence: 99%

The Molecular Machinery of Gametogenesis inGeodiaDemosponges (Porifera): Evolutionary Origins of a Conserved Toolkit across Animals

Koutsouveli

Cárdenas

Santodomingo

et al. 2020

Molecular Biology and Evolution

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“…Analyses of Ihh deficient mice have defined the relation between IHH mutations and BDA1 as disturbed Hh pathway through Ihh signaling leading to truncated limbs [91]. Mutations responsible for BDA1 have been restricted to the N-terminal domain of IHH, and for the most part have altered codon positions 95, 100, and 131 [92,93,94]. The DBA1 mouse model, generated with the use of Ihh point mutated mice, had one of the mutations, E95K, inserted into the mouse Ihh gene locus; the result was that the point mutated mice demonstrated shortened middle phalanges in digits II and V [91].…”

Section: Aberrant Hedgehog Signaling In Skeletal Diseasementioning

confidence: 99%

Recent Insights into Long Bone Development: Central Role of Hedgehog Signaling Pathway in Regulating Growth Plate

Haraguchi

Kitazawa

Kohara

et al. 2019

IJMS

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The longitudinal growth of long bone, regulated by an epiphyseal cartilaginous component known as the “growth plate”, is generated by epiphyseal chondrocytes. The growth plate provides a continuous supply of chondrocytes for endochondral ossification, a sequential bone replacement of cartilaginous tissue, and any failure in this process causes a wide range of skeletal disorders. Therefore, the cellular and molecular characteristics of the growth plate are of interest to many researchers. Hedgehog (Hh), well known as a mitogen and morphogen during development, is one of the best known regulatory signals in the developmental regulation of the growth plate. Numerous animal studies have revealed that signaling through the Hh pathway plays multiple roles in regulating the proliferation, differentiation, and maintenance of growth plate chondrocytes throughout the skeletal growth period. Furthermore, over the past few years, a growing body of evidence has emerged demonstrating that a limited number of growth plate chondrocytes transdifferentiate directly into the full osteogenic and multiple mesenchymal lineages during postnatal bone development and reside in the bone marrow until late adulthood. Current studies with the genetic fate mapping approach have shown that the commitment of growth plate chondrocytes into the skeletal lineage occurs under the influence of epiphyseal chondrocyte-derived Hh signals during endochondral bone formation. Here, we discuss the valuable observations on the role of the Hh signaling pathway in the growth plate based on mouse genetic studies, with some emphasis on recent advances.

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“…Investigations into neural crest cell dynamics and Hh signaling have elucidated its crucial role in craniofacial development and skeletal formation [ 16 ]. The mutation in the Ihh variant alters Gli1–DNA binding patterns and weakens cellular proliferation and migration processes, thereby deepening our understanding of the pathogenesis of Brachydactyly type A1 (BDA1) and the involvement of Ihh signaling in cartilage development [ 17 ]. Additionally, it is reported that Ihh signaling plays a critical role in mediating hypertrophy in both mesenchymal stem cells (MSCs) and human articular chondrocytes [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Hedgehog Signaling Controls Chondrogenesis and Ectopic Bone Formation via the Yap-Ihh Axis

Cong,

Yang

2024

Biomolecules

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Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder characterized by abnormal bone formation due to ACVR1 gene mutations. The identification of the molecular mechanisms underlying the ectopic bone formation and expansion in FOP is critical for the effective treatment or prevention of HO. Here we find that Hh signaling activation is required for the aberrant ectopic bone formation in FOP. We show that the expression of Indian hedgehog (Ihh), a Hh ligand, as well as downstream Hh signaling, was increased in ectopic bone lesions in Acvr1R206H; ScxCre mice. Pharmacological treatment with an Ihh-neutralizing monoclonal antibody dramatically reduced chondrogenesis and ectopic bone formation. Moreover, we find that the activation of Yap in the FOP mouse model and the genetic deletion of Yap halted ectopic bone formation and decreased Ihh expression. Our mechanistic studies showed that Yap and Smad1 directly bind to the Ihh promoter and coordinate to induce chondrogenesis by promoting Ihh expression. Therefore, the Yap activation in FOP lesions promoted ectopic bone formation and expansion in both cell-autonomous and non-cell-autonomous manners. These results uncovered the crucial role of the Yap-Ihh axis in FOP pathogenesis, suggesting the inhibition of Ihh or Yap as a potential therapeutic strategy to prevent and reduce HO.

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p.E95K mutation in Indian hedgehog causing brachydactyly type A1 impairs IHH/Gli1 downstream transcriptional regulation

Cited by 7 publications

References 53 publications

The Molecular Machinery of Gametogenesis inGeodiaDemosponges (Porifera): Evolutionary Origins of a Conserved Toolkit across Animals

The Molecular Machinery of Gametogenesis inGeodiaDemosponges (Porifera): Evolutionary Origins of a Conserved Toolkit across Animals

Recent Insights into Long Bone Development: Central Role of Hedgehog Signaling Pathway in Regulating Growth Plate

Hedgehog Signaling Controls Chondrogenesis and Ectopic Bone Formation via the Yap-Ihh Axis

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