Biology subjects

Godbole, G.

Publications and source records attributed to Godbole, G..

4 recordsLinked to original sources

bioRxiv2025

HOXA10 is a Temporal Switch in Controlling Decidual Inflammation and Its Dysregulation is Associated with Early Pregnancy Loss

Successful implantation requires precisely timed endometrial inflammation. Although an initial inflammatory burst is essential for implantation, this response must be rapidly resolved for placentation and pregnancy to progress. The mechanisms that coordinate this temporal switch remain poorly understood. Here, we identify the transcription factor HOXA10 as a key regulator of inflammatory transitions in decidual stromal cells and examine how its dysregulation contributes to implantation failure and early pregnancy loss. In mice, HOXA10 expression decreases transiently at implantation and rises again post-implantation. Silencing HOXA10 in human decidualized stromal cells induced a robust pro-inflammatory state, altered integrin and cytoskeletal gene expression, and impaired stromal substrate adhesion. In non-pregnant Hoxa10 hypomorphs, stromal cells exhibited elevated IL1β and TXNIP, activation of the NLRP3/ASC inflammasome, and dysregulation of receptivity markers. During pregnancy, persistent HOXA10 deficiency prevented the resolution of inflammation, resulting in disorganized decidua, defective placentation, infertility, or progressive reproductive decline. To assess translational relevance, we analyzed publicly available bulk and single-cell RNA-seq datasets from first-trimester human decidua and from women with recurrent pregnancy loss (RPL). Single-cell analysis revealed that HOXA10 is selectively low in inflammatory decidual stromal cell clusters, which display concordant upregulation of IL1B, PYCARD, TXNIP, and inflammasome components. Consistently, both bulk and single-cell datasets from women with RPL showed reduced HOXA10 accompanied by increased inflammatory gene expression. Overall, HOXA10 functions as a temporal switch that enables the initial inflammatory activation required for implantation and subsequently suppresses inflammation to support decidual organization, adhesion, and placentation. Loss of this switch leads to persistent decidual inflammation and is associated with pregnancy loss in both mouse models and humans. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/691844v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@ee81b6org.highwire.dtl.DTLVardef@85d84eorg.highwire.dtl.DTLVardef@13c1b6aorg.highwire.dtl.DTLVardef@12bed9b_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2020

An early cortical progenitor-specific mechanism regulates thalamocortical innervation

The cortical subplate is critical in regulating the entry of thalamocortical sensory afferents into the cortex. These afferents reach the subplate at embryonic day (E)15.5 in the mouse, but "wait" for several days, entering the cortical plate postnatally. We report that when transcription factor Lhx2 is lost in E11.5 cortical progenitors, which give rise to subplate neurons, thalamocortical afferents display premature, exuberant innervation of the E15.5 cortex. Embryonic mutant subplate neurons are correctly positioned below the cortical plate, but they display an altered transcriptome and immature electrophysiological properties during the waiting period. The sensory thalamus in these cortex-specific Lhx2 mutants displays atrophy, eventually leading to severe deficits in thalamocortical innervation. Strikingly, these phenotypes do not manifest if Lhx2 is lost in postmitotic subplate neurons. These results demonstrate a mechanism operating in subplate progenitors that has profound consequences on the growth of thalamocortical axons into the cortex.

neuroscience↗

bioRxiv2020

An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity

Protein cofactor Ldb1 regulates cell fate specification by interacting with LIM-homeodomain (LIM-HD) proteins in a tetrameric complex consisting of an LDB:LDB dimer that bridges two LIM-HD molecules, a mechanism first demonstrated in the Drosophila wing disc. Here, we demonstrate conservation of this interaction in the regulation of mammalian hippocampal development, which is profoundly defective upon loss of either Lhx2 or Ldb1. Electroporation of a chimeric construct that encodes the Lhx2-HD and Ldb1-DD (dimerization domain) in a single transcript cell-autonomously rescues a comprehensive range of hippocampal deficits in the mouse Ldb1 mutant, including the acquisition of field-specific molecular identity and the regulation of the neuron-glia cell fate switch. This demonstrates that the LHX:LDB complex is an evolutionarily conserved molecular regulatory device that controls complex aspects of regional cell identity in the developing brain. Summary statementSimilar to an Apterous-Chip mechanism that patterns the Drosophila wing blade, interaction between mammalian orthologs Lhx2 and Ldb1 regulates multiple aspects of hippocampal development in the mouse.

neuroscience↗

bioRxiv2019

A real-time PCR for the differentiation of typhoidal and non-typhoidal Salmonella

Rapid and accurate differentiation of Salmonella spp. causing enteric fever from non-typhoidal Salmonella is essential for clinical management of cases, laboratory risk management and implementation of public health measures. Current methods used for confirmation of identification including biochemistry and serotyping as well as whole genome sequencing analyses, takes several days. Here we report the development and evaluation of a real-time PCR assay that can be performed directly on crude DNA extracts from bacterial colonies, for the rapid identification of typhoidal and non-typhoidal Salmonella. This novel two-hour assay identifies the genus Salmonella by detecting the ttr gene, encoding tetrathionate reductase, and defines typhoidal Salmonella by the detection of S. Typhi and Paratyphi-specific gene combinations. PCR assay performance was determined using 211 clinical cultures of Salmonella (114 non-typhoidal and 97 Typhoidal strains) and 7 clinical non-Salmonella cultures. In addition, the specificity of the assay was evaluated in silico using a diverse in-house collection of 1882 Salmonella whole genome sequences. The real-time PCR results for 218 isolates and the genomic analysis of the 1882 isolates produced 100% sensitivity and 100% specificity (based on a 7 gene profile) for identifying typhoidal Salmonella compared to the Salmonella whole genome sequening identification methods currently used at Public Health England. This paper describes a robust real-time PCR assay for the rapid, accurate identification of typhoidal and non-typhoidal Salmonella which will be invaluable for the urgent screening of isolates from symptomatic individuals, the safe processing of isolates in laboratories and for assisting the management of public health risks.

microbiology↗