Flowers are icons in developmental studies of complex structures. The vast majority of 250,000 angiosperm plant species have flowers with a conserved organ plan bearing sepals, petals, stamens, and ...carpels in the center. The combinatorial model for the activity of the so-called ABC homeotic floral genes has guided extensive experimental studies in Arabidopsis thaliana and many other plant species. However, a mechanistic and dynamical explanation for the ABC model and prevalence among flowering plants is lacking. Here, we put forward a simple discrete model that postulates logical rules that formally summarize published ABC and non-ABC gene interaction data for Arabidopsis floral organ cell fate determination and integrates this data into a dynamic network model. This model shows that all possible initial conditions converge to few steady gene activity states that match gene expression profiles observed experimentally in primordial floral organ cells of wild-type and mutant plants. Therefore, the network proposed here provides a dynamical explanation for the ABC model and shows that precise signaling pathways are not required to restrain cell types to those found in Arabidopsis, but these are rather determined by the overall gene network dynamics. Furthermore, we performed robustness analyses that clearly show that the cell types recovered depend on the network architecture rather than on specific values of the model's gene interaction parameters. These results support the hypothesis that such a network constitutes a developmental module, and hence provide a possible explanation for the overall conservation of the ABC model and overall floral plan among angiosperms. In addition, we have been able to predict the effects of differences in network architecture between Arabidopsis and Petunia hybrida.
This study investigates a unique and complex eye phenotype characterized by minimal iris defects, foveal hypoplasia, optic nerve coloboma, and severe posterior segment damage. Through genetic ...analysis and bioinformatic tools, a specific nonsynonymous substitution, p.(Asn114Ser), within the PAX6 gene’s paired domain is identified. Although this substitution is not in direct contact with DNA, its predicted stabilizing effect on the protein structure challenges the traditional understanding of PAX6 mutations, suggesting a gain-of-function mechanism. Contrary to classical loss-of-function effects, this gain-of-function hypothesis aligns with research demonstrating PAX6’s dosage sensitivity. Gain-of-function mutations, though less common, can lead to diverse phenotypes distinct from aniridia. Our findings emphasize PAX6’s multifaceted influence on ocular phenotypes and the importance of genetic variations. We contribute a new perspective on PAX6 mutations by suggesting a potential gain-of-function mechanism and showcasing the complexities of ocular development. This study sheds light on the intricate interplay of the genetic alterations and regulatory mechanisms underlying complex eye phenotypes. Further research, validation, and collaboration are crucial to unravel the nuanced interactions shaping ocular health and development.
is a fungal pathogen that claims hundreds of thousands of lives annually. Targeted genetic manipulation through biolistic transformation in
drove the investigation of this clinically important ...pathogen at the molecular level. Although costly and inefficient, biolistic transformation remains the major method for editing the
genome as foreign DNAs introduced by other methods such as electroporation are predominantly not integrated into the genome. Although the majority of DNAs introduced by biolistic transformation are stably inherited, the transformation efficiency and the homologous integration rate (∼1-10%) are low. Here, we developed a
nsient
RISPR (clustered regularly interspaced short palindromic repeat)-Cas9 coupled with
lectroporation (TRACE) system for targeted genetic manipulations in the
species complex. This method took advantages of efficient genome integration due to double-strand breaks created at specific sites by the transient CRISPR-Cas9 system and the high transformation efficiency of electroporation. We demonstrated that TRACE can efficiently generate precise single-gene deletion mutants using the
locus as an example. This system can also effectively delete multiple genes in a single transformation, as evident by the successful generation of quadruple
α
Δ
Δ
Δ
Δ mutants. In addition to generating gene deletion mutants, we complemented the
Δ mutant by integrating a wild-type
allele at the "safe haven" region (
) via homologous recombination using TRACE. Interestingly, introduced DNAs can be inserted at a designated genetic site without any homologous sequences, opening up numerous other applications. We expect that TRACE, an efficient, versatile, and cost-effective gene editing approach, will greatly accelerate research in this field.
ETV6::ABL1 gene fusion is a rare recurrent genomic rearrangement associated with hematologic malignancies, and frequently occurs with additional anomalies. Due to the opposite chromosome orientations ...of the ETV6 and ABL1 genes, an oncogenic in-frame ETV6::ABL1 gene fusion cannot be formed by a simple translocation. The molecular mechanism of the ETV6::ABL1 fusion and the significance of co-occurring anomalies are not fully understood. We characterized genomic alterations in an individual with ETV6::ABL1 gene-fusion-positive myeloid neoplasm using various genomic technologies. Our findings uncovered a molecular mechanism of the ETV6::ABL1 fusion, in which a paracentric inversion within the short arm of chromosome 12 (12p) and a translocation between the long arm of a chromosome 9 and the 12p with the inversion were involved. In addition, we detected multiple additional anomalies in the individual, and our findings suggested that the ETV6::ABL1 fusion occurred as a secondary event in a subset of cells with the additional anomalies. We speculate that the additional anomalies may predispose to further pathogenic changes, including ETV6::ABL1 fusion, leading to neoplastic transformation.
White rust Albugo candida (Pers. Ex. Lev) Kuntze is an important oomycetes disease of Indian mustard Brassica juncea (L.) Czern & Coss that causes a drastic reduction in seed yield and quality when ...the conditions are favorable. A set of 25 Indian mustard genotypes were screened against A. candida Delhi isolate (Ac-Dli) under both controlled and natural epiphytotic conditions. Out of 25, only six genotypes (Pusa Karishma, PDZ-3, Heera, BEC-144, BIO YSR, and Donskaja) were found highly resistant in both environments. To study the inheritance of resistance, four resistant genotypes (BEC-144, BIO YSR, Pusa Karishma, and Donskaja) were crossed with three susceptible genotypes (PM-24, Pusa Vijay, and MSTWR-17-15) in a definite design. The parents, Fsub.1, Fsub.2, and BCsub.1Fsub.1 (Fsub.1 backcrossed with susceptible parent) generations were screened under both artificially controlled and natural epiphytotic conditions and the results indicated that the resistance in BIO YSR, BEC-144, and Pusa Karishma is governed by a single dominant gene, but more than one dominant gene is responsible for resistance in Donskaja. A test of an allelism conducted on the Fsub.2 population derived by crossing resistant (BEC-144) × resistant (BIO YSR) genotypes indicated that the gene imparting resistance to Ac-Dli isolate in the resistant parents BEC-144 and BIO YSR is the same and they are allelic to each other. Therefore, in broader terms, the information generated in the present study will be useful in Indian mustard breeding programs for the development of durable resistant cultivars.
The evolutionarily conserved p53 protein and its cellular pathways mediate tumour suppression through an informed, regulated and integrated set of responses to environmental perturbations resulting ...in either cellular death or the maintenance of cellular homeostasis. The p53 and MDM2 proteins form a central hub in this pathway that receives stressful inputs via MDM2 and respond via p53 by informing and altering a great many other pathways and functions in the cell. The MDM2-p53 hub is one of the hubs most highly connected to other signalling pathways in the cell, and this may be why TP53 is the most commonly mutated gene in human cancers. Initial or truncal TP53 gene mutations (the first mutations in a stem cell) are selected for early in cancer development inectodermal and mesodermal-derived tissue-specific stem and progenitor cells and then, following additional mutations, produce tumours from those tissue types. In endodermal-derived tissue-specific stem or progenitor cells, TP53 mutations are functionally selected as late mutations transitioning the mutated cell into a malignant tumour. The order in which oncogenes or tumour suppressor genes are functionally selected for in a stem cell impacts the timing and development of a tumour.
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