Biology subjects

Consonni, G.

Publications and source records attributed to Consonni, G..

4 recordsLinked to original sources

bioRxiv2025

Mesodermal-specific MECP2 expression in Drosophila induces visceral and skeletal muscle defects rescued by butyrate supplementation

BackgroundPatients affected by Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) experience disabling muscle weakness and gastrointestinal dysmotility of unclear origin. Whether these defects arise cell-autonomously, rather than secondarily to neural dysfunction, and which developmental windows are most vulnerable to MeCP2 disfunction remains unresolved. MeCP2 is a dosage-sensitive transcriptional regulator, whose functions are tightly linked to chromatin states. Because short-chain fatty acids (SCFAs) are known to inhibit histone deacetylases (HDACs), a tractable in vivo model is needed to test the effect of HDAC modulation on muscle defects. MethodsWe misexpressed human MECP2 in the Drosophila melanogaster mesoderm that gives rise to skeletal and visceral muscles. We analyzed quantitatively their morphology and function. To assess the effects of SCFA supplementation, we also supplemented diets with sodium butyrate (NaB), Lalbaay(R), a NaB-containing supplement, acetate (AcOH), and valproate (VPA). FindingsMECP2 misexpression caused pre-eclosion lethality, thinning of larval skeletal fibers with nuclear mispositioning and altered mitochondria. Functionally, it reduced locomotion, decreased food transit and gut peristalsis. Phenotypes were strongest when expression began during development. NaB and VPA supplementation rescue most of these phenotypes, consistent with their histone-deacetylase (HDAC) activity. Defects were not observed upon comparable misexpression of an RTT-associated MeCP2 loss-of-function variant, indicating that they might be relevant to pathogenesis of MECP2-related disorders. InterpretationOur genetic in vivo analysis models peripheral effects of MeCP2 dysregulation and their amelioration, supporting the possibility of HDAC-targeted strategies for MECP2-related muscle and gastrointestinal dysfunction.

genetics↗

bioRxiv2024

Genetic interaction between GL15 and FDL1 modulates juvenile cuticle deposition and leaf permeability in maize

The plant cuticle is a hydrophobic layer that serves as the primary barrier between plant surfaces and the external environment, limiting water loss and protecting against various stresses. This study investigates the genetic interaction between the maize ZmFDL1 and ZmGL15 genes and their role in modulating juvenile cuticle deposition and leaf permeability. The research was undertaken to understand how these genes influence cuticle composition and structure, which are crucial for plant protection against environmental stresses such as drought. We analysed the chemical composition of cutin and waxes, as well as cuticle-dependent leaf permeability. Our findings reveal that ZmFDL1 and ZmGL15 individually and synergically regulate the deposition of cuticular components, with significant impacts on leaf permeability. The gl15-S mutant exhibited an adult-like cuticle with higher cutin and lower wax contents, leading to reduced leaf permeability and improved water retention under drought conditions. These results highlight the importance of cutin in forming an effective water barrier and suggest that modulating cuticle composition with enhanced cutin content could be a strategy for improving drought tolerance in crops. This study provides new insights into the genetic regulation of cuticle biosynthesis and its relevance for plant adaptation to water scarcity. HighlightO_LIZmFDL1 and ZmGL15 interact to modulate cuticle composition and reduce leaf water loss. C_LIO_LIZmFDL1 and ZmGL15 genes regulate juvenile cuticle deposition in maize. C_LIO_LIThe gl15-S mutant shows an adult-like cuticle with higher cutin and lower wax contents. C_LIO_LIThe gl15-S mutation is epistatic to fdl1-1, partially rescuing the defective fdl1 cuticle phenotype. C_LIO_LIThe cuticle composition in gl15-S mutants leads to reduced leaf permeability and improved water retention under drought conditions. C_LIO_LICuticular layer with enhanced cutin content could improve drought tolerance in crops. C_LI

genetics↗

bioRxiv2023

Gut barrier defects, increased intestinal innate immune response, and enhanced lipid catabolism drive lethality in N-glycanase 1 deficient Drosophila

Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of infectious versus non-infectious mechanisms on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) leads to gut barrier defects, which cause starvation and increased JNK activity. These defects result in Foxo overactivation, which induces a hyperactive innate immune response and lipid catabolism, thereby contributing to lethality associated with loss of Pngl. Notably, germ-free rearing of Pngl mutants did not rescue lethality. In contrast, raising Pngl mutants on isocaloric, fat-rich diets improved animal survival in a dosage-dependent manner. Our data indicate that Pngl functions in Drosophila larvae to establish the gut barrier, and that the immune and metabolic consequences of loss of Pngl are primarily mediated through non-infectious mechanisms.

developmental biology↗

bioRxiv2020

The drought-responsive ZmFDL1 gene regulates cuticle biosynthesis and cuticle-dependent leaf permeability

In higher plants, the outer surface of the aerial parts is covered by the cuticle, a complex lipid layer that constitutes a barrier against damages caused by environmental factors and provides protection against non-stomatal water loss. We show in this study that cuticle deposition, during the juvenile phase of in maize (Zea mays) plant development, and cuticle-dependent leaf permeability are controlled by the MYB transcription factor ZmMYB94/FUSED LEAVES1 (ZmFDL1). Biochemical analysis showed that in fdl1-1 mutant seedlings at the coleoptile stage both cutin and wax biosynthesis and deposition were altered. Among cutin compounds, {omega}-hydroxy fatty acids and polyhydroxy-fatty acids were specifically affected, while the reduction of epicuticular waxes, was mainly observed in primary long chain alcohols, and to a minor extent, long-chain wax esters. Transcriptome analysis allowed the identification of novel candidate genes involved in lipid metabolism and the assembly of a proposed pathway for cuticle biosynthesis in maize. Lack of ZmFDL1 affects the expression of genes located in different modules of the pathway and correspondence between gene transcriptional variations and biochemical defects have been highlighted. A decrease in cuticle-dependent leaf permeability was observed in maize seedlings exposed to drought as well as ABA treatment, which implies coordinated changes in the transcript levels of ZmFDL1 and associated genes. Overall, our results suggest that the response to water stress implies the activation of wax biosynthesis and the involvement of by both ZmFDL1 and ABA regulatory pathways. One-Sentence SummaryCuticle biosynthesis and cuticle-mediated drought-response during the juvenile phase of maize plant growth, are regulated by the MYB transcription factor fused leaves1 (ZmFDL1) and influenced by ABA.

plant biology↗