Biology subjects

Shankar, M.

Publications and source records attributed to Shankar, M..

5 recordsLinked to original sources

bioRxiv2026

Transposon-associated genetic structure of a fungal phytopathogen population of wheat

Septoria nodorum blotch (SNB) is an economically important fungal disease of wheat caused by Parastagonospora nodorum. It is primarily controlled by the breeding of resistant wheat cultivars, but experience over the last 50 years shows that new pathogen populations soon evolve that are more virulent on the current popular cultivars. In this study, we assembled a panel of 360 P. nodorum isolates. The collection resolved into eight subpopulations. One core and seven transient populations were found possessing contrasting characters in term of spatial and temporal distribution, mating-type, effector haplotypes and patterns of intact and degraded copies of a Tc-1 mariner transposon, called Molly. Molly can proliferate and randomly insert throughout the fungal genome. Its multiplication in sexual population likely triggered RIP which partially explains the extensive genetic diversity and explains the ability to form new adapted lineages and the observed population structure of this important pathogen of wheat. When tested on wheat, the recently emerged groups exhibited greater pathogenicity on modern elite cultivars consistent with the low-amplitude boom-and-bust cycle observed previously. It is possible that active copies of Molly transpose and contribute to both the birth and death of the transient groups. This study identified and characterised a fungal specific transposable element (TE) which plays a vital role in shaping Australian P. nodorum population structure and creating extensive genetic diversity which potentially leads to the pathogens better adaptation. The study suggests practical measures to improve the efficiency and longevity of resistance breeding for SNB.

pathology↗

bioRxiv2026

Progenitor Diversity and Architecture of the Human Ganglionic Eminences Shaping the Basal Ganglia

The embryonic medial and lateral ganglionic eminences (MGE, LGE) are the principal sources of most neurons and glia for the basal ganglia. In primates, the MGE has a distinctive cytoarchitecture characterized by doublecortin enriched cellular nests (DENs), yet the architectonic organization underlying DEN formation, the molecular heterogeneity of ganglionic eminence progenitors and their lineage relationships, remain poorly understood. Here, using paired single-nucleus transcriptomics and chromatin accessibility profiling of the three GEs, we identify distinct progenitor populations, delineate their gene regulatory networks, and reconstruct their lineage trajectories. Live imaging reveals a unipolar outer radial glia-like population (GE-oRG) that undergoes mitotic somal translocation. Spatial transcriptomics identifies a distinct CRABP1+/ANGPT2+ domain within the MGE. Integrated spatial and electron microscopy demonstrates a periphery-to-center gradient of differentiation in the MGE. Leveraging DEN-forming MGE organoids derived from PCDH19 knockout human pluripotent stem cell lines, we identify the protocadherin, PCDH19, as a key regulator of DEN formation.

neuroscience↗

bioRxiv2025

α7 nicotinic acetylcholine receptors regulate radial glia fate in the developing human cortex

Prenatal nicotine exposure impairs fetal cortical grey matter volume, but the precise cellular mechanisms remain poorly understood. This study elucidates the role of nicotinic acetylcholine receptors (nAChRs) in progenitor cells and radial glia (RG) during human cortical development. We identify two nAChR subunits--CHRNA7 and the human-specific CHRFAM7A--expressed in SOX2+ progenitors and neurons, with CHRFAM7A particularly enriched along RG endfeet. nAChR activation in organotypic slices and dissociated cultures increases RG proliferation while decreasing neuronal differentiation, whereas nAChR knockdown reduces RG and increases neurons. Single-cell RNA sequencing reveals that nicotine exposure downregulates key genes in excitatory neurons (ENs), with CHRNA7 or CHRFAM7A selectively modulating these changes, suggesting an evolutionary divergence in regulatory pathways. Furthermore, we identify YAP1 as a critical downstream effector of nAChR signaling, and inhibiting YAP1 reverses nicotine-induced phenotypic alterations in oRG cells, highlighting its role in nicotine-induced neurodevelopmental pathophysiology.

neuroscience↗

bioRxiv2020

Timed mesodermal FGF and BMP govern the multi-step thyroid specification

Thyroid tissue is the site for de novo synthesis of thyroid hormones which are essential for vertebrate development and growth. Defects in embryonic thyroid morphogenesis are a predominant cause for congenital thyroid diseases but the molecular pathomechanisms are incompletely understood. The first molecularly recognizable step of thyroid development is the specification of thyroid precursors at a defined position in the anterior foregut endoderm. While recent studies identified FGF and BMP pathways as critical signaling factors for thyroid specification, the interplay between extrinsic signaling cues and thyroid transcription factor expression remained elusive. Here, we used zebrafish embryos to decipher the dynamics of thyroid transcription factor induction in relation to FGF and BMP signaling activities in pharyngeal endoderm. We first identified a previously unrecognized endodermal thyroid progenitor cell population expressing Pax2a but not Nkx2.4b. This cell population is characterized by enhanced FGF signaling but initially lacks detectable BMP signaling. A subpopulation of Pax2a-expressing progenitors differentiates subsequently into thyroid lineage-committed precursor cells co-expressing Pax2a and Nkx2.4b. We next combined pharmacological approaches with genetic models permitting inhibition or ectopic overactivation of signaling pathways to timely manipulate FGF and BMP activities. These experiments support a model where FGF signaling primarily regulates Pax2a expression whereas BMP signaling has dual functions in regulation of both Pax2a and Nkx2.4b expression. Collectively, our data allow us to formulate a refined model of thyroid cell specification from foregut endoderm.

developmental biology↗

bioRxiv2020

Calprotectin modulates inflammatory collateral tissue damage during intraperitoneal origin systemic candidiasis

Peritonitis is a leading cause of severe sepsis in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial, pro-inflammatory protein complex often used as a biomarker for diagnosis of disease activities in many inflammatory disorders. Here we describe the role of S100A8/A9 on inflammatory collateral tissue damage (ICTD). We performed an in vivo Candida albicans disseminated peritonitis mouse model using WT and S100A9-deficient mice and stimulated primary macrophages with recombinant S100A8/A9 in the presence or absence of the compound paquinimod, a specific inhibitor of S100A9. In addition, the effects on ICTD and fungal clearance were investigated. S100A9-deficient mice developed less ICTD than wildtype mice. Restoration of S100A8/A9 in S100A9 knockout mice resulted in increased ICTD and fungal clearance comparable to wildtype levels. Treatment with paquinimod abolished ICTD. The data indicated that S100A8/A9 controls ICTD levels and host antimicrobial modulation at a systemic level during intra-abdominal candidiasis (IAC).

immunology↗