BLADE-ON-PETIOLE interacts with CYCLOIDEA to fine-tune CYCLOIDEA-mediated flower symmetry in monkeyflowers (Mimulus).

Morphological novelties, or key innovations, are instrumental to the diversification of the organisms. In plants, one such innovation is the evolution of zygomorphic flowers, which is thought to promote outcrossing and increase flower morphological diversity. We isolated three allelic mutants from two Mimulus species displaying altered floral symmetry and identified the causal gene as the ortholog of Arabidopsis BLADE-ON-PETIOLE. We found that MlBOP and MlCYC2A physically interact and this BOP-CYC interaction module is highly conserved across the angiosperms. Furthermore, MlBOP self-ubiquitinates and suppresses MlCYC2A self-activation. MlCYC2A, in turn, impedes MlBOP ubiquitination. Thus, this molecular tug-of-war between MlBOP and MlCYC2A fine-tunes the expression of MlCYC2A, contributing to the formation of bilateral symmetry in flowers, a key trait in angiosperm evolution.

A distinct foliar pigmentation pattern formed by activator-repressor gradients upstream of an anthocyanin-activating R2R3-MYB.

The emergence of novel traits is often preceded by a potentiation phase, when all the genetic components necessary for producing the trait are assembled. However, elucidating these potentiating factors is challenging. We have previously shown that an anthocyanin-activating R2R3-MYB, STRIPY, triggers the emergence of a distinct foliar pigmentation pattern in the monkeyflower Mimulus verbenaceus. Here, using forward and reverse genetics approaches, we identify three potentiating factors that pattern STRIPY expression: MvHY5, a master regulator of light signaling that activates STRIPY and is expressed throughout the leaf, and two leaf developmental regulators, MvALOG1 and MvTCP5, that are expressed in opposing gradients along the leaf proximodistal axis and negatively regulate STRIPY. These results provide strong empirical evidence that phenotypic novelties can be potentiated through incorporation into preexisting genetic regulatory networks and highlight the importance of positional information in patterning the novel foliar stripe.

Comparative Analysis of Whole Transcriptome Profiles in Septic Cardiomyopathy: Insights from CLP- and LPS-Induced Mouse Models.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with septic cardiomyopathy being a common and severe complication. Despite its significant clinical impact, the molecular mechanisms underlying sepsis-induced cardiomyopathy (SICM) remain incompletely understood. In this study, we performed a comparative analysis of whole transcriptome profiles using RNA sequencing in mouse hearts in two widely used mouse models of septic cardiomyopathy. CLP-induced sepsis was achieved by surgical cecal ligation and puncture, while LPS-induced sepsis was induced using a 5 mg/kg intraperitoneal (IP) injection of lipopolysaccharide (LPS). For consistency, we utilized sham-operated mice as the control for septic models. Our aim was to identify key genes and pathways involved in the development of septic cardiomyopathy and to evaluate the similarities and differences between the two models. Our findings demonstrated that both the CLP and lipopolysaccharide LPS methods could induce septic heart dysfunction within 24 h. We identified common transcriptional regulatory regions in the septic hearts of both models, such as Nfkb1, Sp1, and Jun. Moreover, differentially expressed genes (DEGs) in comparison to control were involved in shared pathways, including regulation of inflammatory response, regulation of reactive oxygen species metabolic process, and the JAK-STAT signaling pathway. However, each model presented distinctive whole transcriptome expression profiles and potentially diverse pathways contributing to sepsis-induced heart failure. This extensive comparison enhances our understanding of the molecular basis of septic cardiomyopathy, providing invaluable insights. Accordingly, our study also contributes to the pursuit of effective and personalized treatment strategies for SICM, highlighting the importance of considering the specific causative factors.

A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death.

Ischemic stroke causes a heavy health burden worldwide, with over 10 million new cases every year. Despite the high prevalence and mortality rate of ischemic stroke, the underlying molecular mechanisms for the common etiological factors of ischemic stroke and ischemic stroke itself remain unclear, which results in insufficient preventive strategies and ineffective treatments for this devastating disease. In this review, we demonstrate that transient receptor potential cation channel, subfamily M, member 2 (TRPM2), a non-selective ion channel activated by oxidative stress, is actively involved in all the important steps in the etiology and pathology of ischemic stroke. TRPM2 could be a promising target in screening more effective prophylactic strategies and therapeutic medications for ischemic stroke.

The leaf polarity factors SGS3 and YABBYs regulate style elongation through auxin signaling in Mimulus lewisii.

Style length is a major determinant of breeding strategies in flowering plants and can vary dramatically between and within species. However, little is known about the genetic and developmental control of style elongation. We characterized the role of two classes of leaf adaxial-abaxial polarity factors, SUPPRESSOR OF GENE SILENCING3 (SGS3) and the YABBY family transcription factors, in the regulation of style elongation in Mimulus lewisii. We also examined the spatiotemporal patterns of auxin response during style development. Loss of SGS3 function led to reduced style length via limiting cell division, and downregulation of YABBY genes by RNA interference resulted in shorter styles by decreasing both cell division and cell elongation. We discovered an auxin response minimum between the stigma and ovary during the early stages of pistil development that marks style differentiation. Subsequent redistribution of auxin response to this region was correlated with style elongation. Auxin response was substantially altered when both SGS3 and YABBY functions were disrupted. We suggest that auxin signaling plays a central role in style elongation and that the way in which auxin signaling controls the different cell division and elongation patterns underpinning natural style length variation is a major question for future research.

Developmental Genetics of Corolla Tube Formation: Role of the tasiRNA-ARF Pathway and a Conceptual Model.

Over 80,000 angiosperm species produce flowers with petals fused into a corolla tube. The corolla tube contributes to the tremendous diversity of flower morphology and plays a critical role in plant reproduction, yet it remains one of the least understood plant structures from a developmental genetics perspective. Through mutant analyses and transgenic experiments, we show that the tasiRNA-ARF pathway is required for corolla tube formation in the monkeyflower species Mimulus lewisii Loss-of-function mutations in the M. lewisii orthologs of ARGONAUTE7 and SUPPRESSOR OF GENE SILENCING3 cause a dramatic decrease in abundance of TAS3-derived small RNAs and a moderate upregulation of AUXIN RESPONSE FACTOR3 (ARF3) and ARF4, which lead to inhibition of lateral expansion of the bases of petal primordia and complete arrest of the upward growth of the interprimordial regions, resulting in unfused corollas. Using the DR5 auxin-responsive promoter, we discovered that auxin signaling is continuous along the petal primordium base and the interprimordial region during the critical stage of corolla tube formation in the wild type, similar to the spatial pattern of MlARF4 expression. Auxin response is much weaker and more restricted in the mutant. Furthermore, exogenous application of a polar auxin transport inhibitor to wild-type floral apices disrupted petal fusion. Together, these results suggest a new conceptual model highlighting the central role of auxin-directed synchronized growth of the petal primordium base and the interprimordial region in corolla tube formation.