Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1000498 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25475742_1.fastq.gz | Fastqsanger.gz | |||
| SRR25475742_2.fastq.gz | Fastqsanger.gz | |||
| SRR25475743_1.fastq.gz | Fastqsanger.gz | |||
| SRR25475743_2.fastq.gz | Fastqsanger.gz | |||
| SRR25475744_1.fastq.gz | Fastqsanger.gz |
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Project description:The specification and maintenance of distinct zones of chondrocytes within growth plates and joints ensures proper skeletal development through adulthood. Rare mutations in the transcription factor NKX3.2 underlie Spondylo-megaepiphyseal-metaphyseal dysplasia (SMMD), which is characterized by skeletal defects including scoliosis, large epiphyses, wide growth plates, and supernumerary joints in the distal limbs. Embryonic knockdown of nkx3.2 function in zebrafish had revealed a requirement in jaw joint specification, yet embryonic lethality of nkx3.2 knockdown zebrafish and mouse Nkx3.2 mutants had precluded an analysis of post-embryonic functions. Here we report adult viable nkx3.2 zebrafish mutants that display ectopic cartilage overgrowth in place of a missing jaw joint, as well as severe dysmorphologies of the facial skeleton, skullcap, and spine. We also isolate rare viable nkx3.2 knockdown animals that lack the jaw joint but fail to display ectopic cartilage growth and scoliosis, indicating post-embryonic roles for Nkx3.2 beyond jaw joint specification. Consistently, we observe nkx3.2 expression in the subarticular zone of the adult jaw joint and in pre-hypertrophic growth plate chondrocytes. Single-cell RNA sequencing reveals an upregulation of stress-induced pathways in mutants, including the prostaglandin D2 synthase ptgdsb.1 and the mTOR regulator sestrin1, which we confirm by in situ RNA analysis of the defective jaw joint region. Our data reveal a zebrafish model for the joint and spine defects of SMMD and point to post-embryonic roles for Nkx3.2 in buffering the stress response and dampening proliferation in joint-adjacent chondrocytes.
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Project description:The jaws are complementary in form and function but develop asymmetrically, as the lower but not upper jaw bone forms around a prominent cartilage template. How such differences in skeletal composition are patterned is unclear. Here, we identify four Nuclear receptor 2f genes, nr2f1a, nr2f1b, nr2f2, and nr2f5, as enriched in zebrafish upper jaw precursors. Whereas loss of Nr2f genes results in expansion of upper jaw cartilage to resemble that of the lower jaw, Nr2f5 misexpression inhibits lower jaw cartilage formation. Genome-wide analyses show that Nr2f genes prevent expansion of lower jaw-associated gene expression into the upper jaw territory. Further, restriction of Nr2f expression by Endothelin1 signaling is critical for lower jaw development, as reducing Nr2f dosage fully restores lower jaw development in edn1 mutants. We propose that Nr2f genes drive jaw asymmetry by limiting early cartilage differentiation in the upper jaw to preserve more precursors for later osteogenesis.
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Project description:Phosphate (Pi) is an essential element to all living cells yet fluctuations in Pi concentrations are recurrent in the marine environment. Diatoms are amongst the most successful phytoplankton clade living in the worldâs oceans adapting to and surviving long periods of sub-optimal conditions and resuming growth as soon as nutrient concentrations permit. The knowledge of the molecular underpinnings of diatom ecological success is, however, still very incomplete. Using high-throughput RNA sequencing we have identified the dynamics of the model diatom Phaeodactylum tricornutum global transcriptome in response to Pi fluctuations. We report genes encoding previously unidentified putative Pi transporters that, together with the alkaline phosphatases genes highly expressed under Pi depletion, are probably accountable for a very efficient Pi scavenging system. Our data also reveal the complexity of the P. tricornutum responsive sensory and signaling system that combines bacterial two-component systems with more complex pathways reminiscent of metazoans. This intricate set of membrane receptors and signal-transduction related proteins is likely responsible for the detection of environmental nutrient fluctuations, triggering a multitude of signaling cascades leading to gene regulatory events that define new adaptive physiological states. This together with the novel detection of a multitude of long non-coding intergenic RNAs specifically expressed under Pi stress, begins to provide insights into the complex molecular regulatory program involved in the resilience and ecological success of diatoms. Examination of Pi-responsive transcriptoms in diatoms.
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Project description:The 3' untranslated regions (3' UTRs) of mRNAs play important roles in the regulation of mRNA localization, translation, and stability. Alternative cleavage and polyadenylation (APA) generates mRNAs with different 3' UTRs, but the involvement of this process in stress response has not been clarified. Here, we report that a subset of stress-related genes exhibits 3' UTR extensions of their mRNAs during dehydration stress. These extended 3' UTRs have characteristics of long noncoding RNAs and likely do not interact with miRNAs. Functional studies using T-DNA insertion mutants reveal that they can function as antisense transcripts to repress expression levels of sense genes from the opposite strand, or can activate the transcription of downstream genes from the same strand. Poly(A) signal analysis reveal that mRNAs with 3' UTR extensions have weaker poly(A) signals than mRNAs without 3' UTR extensions. Finally, we show that their biogenesis is partially dependent on a trans-acting factor FPA. Taken together, we report that dehydration stress could induce mRNA 3' UTR extensions, and elucidate a novel function for these stress-induced 3' UTR extensions as long noncoding RNAs in the regulation of their neighboring genes.
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