Biology subjects

Samanta, J.

Publications and source records attributed to Samanta, J..

6 recordsLinked to original sources

bioRxiv2024

Select Bacterial Species Establish and Maintain Functionally Essential pH Gradient Profile within the Mosquito Larval Gut

The unique pH profile of mosquito larval midgut including the highly alkaline anterior midgut (AMG) and its significance in digestive physiology has been known for a long time. More recently, metagenomic association studies have shown that diverse assemblage of bacteria (microbiota) present in the gut influence larval nutrition, growth, development, and several other physiological processes. However, the precise functional mechanisms of these host-microbe interactions remain poorly understood. In this research, we studied the functional significance of gut associated bacteria in larval growth utilizing Aedes albopictus axenic/ gnotobiotic model. Results of our study demonstrate that, for AMG alkalinization, concurrent presence of Carbonic Anhydrase (CA) activity and live bacteria is essential and that the later could not be substituted by either cell-free bacterial culture supernatant, or bacterial cell lysate. Further, we found that the gut pH profile and presence of proteolytic activity could be observed in larvae colonized only with select members of the microbiota that are capable of secreting extracellular protease. Collectively, our findings suggest a novel and interesting evolutionary mechanism of host-microbe interaction, in which select members of the gut microbiota promote larval nutrition, growth and development by providing protease and creating ionic microenvironment optimal for its activity.

microbiology↗

bioRxiv2023

Wobbly hedgehog syndrome- a progressive neurodegenerative disease

Wobbly hedgehog syndrome (WHS) has been long considered to be a myelin disease primarily affecting the four-toed hedgehog. In this study, we have shown for the first time that demyelination is accompanied by extensive remyelination in WHS. However, remyelination is not enough to compensate for the axonal degeneration and neuronal loss, resulting in a progressive neurodegenerative disease reminiscent of progressive forms of multiple sclerosis (MS) in humans. Thus, understanding the pathological features of WHS may shed light on the disease progression in progressive MS and ultimately help to develop therapeutic strategies for both diseases. HighlightsO_LIWobbly hedgehog syndrome (WHS) is a progressive neurodegenerative disease. C_LIO_LISpongy degeneration of the brain and spinal cord is the diagnostic feature of WHS. C_LIO_LIWHS affected brain and spinal cord show extensive demyelination and remyelination. C_LIO_LIAxonal degeneration is accompanied by loss of neurons in WHS. C_LI O_FIG O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/547983v1_figu1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@cb6155org.highwire.dtl.DTLVardef@634d4dorg.highwire.dtl.DTLVardef@1681726org.highwire.dtl.DTLVardef@c80123_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

neuroscience↗

bioRxiv2021

Gli1 regulates the postnatal acquisition of peripheral nerve architecture

Peripheral nerves are organized into discrete cellular compartments. Axons, Schwann cells (SCs), and endoneurial fibroblasts (EFs) reside within the endoneurium and are surrounded by the perineurium - a cellular sheath comprised of layers of perineurial glia (PNG). SC secretion of Desert Hedgehog (Dhh) regulates this organization. In Dhh nulls, the perineurium is deficient and the endoneurium is subdivided into small compartments termed minifascicles. Human Dhh mutations cause a peripheral neuropathy with similar defects. Here we examine the role of Gli1, a canonical transcriptional effector of hedgehog signaling, in regulating peripheral nerve organization. We identify PNG, EFs, and pericytes as Gli1-expressing cells by genetic fate mapping. Although expression of Dhh by SCs and Gli1 in target cells is coordinately regulated with myelination, Gli1 expression unexpectedly persists in Dhh null EFs. Thus, Gli1 is expressed in EFs non-canonically i.e., independent of hedgehog signaling. Gli1 and Dhh also have non-redundant activities. In contrast to Dhh nulls, Gli1 nulls have a normal perineurium. Like Dhh nulls, Gli1 nulls form minifascicles, which we show likely arise from EFs. Thus, Dhh and Gli1 are independent signals: Gli1 is dispensable for perineurial development but functions cooperatively with Dhh to drive normal endoneurial development. During development, Gli1 also regulates endoneurial extracellular matrix production, nerve vascular organization, and has modest, non-autonomous effects on SC sorting and myelination of axons. Finally, in adult nerves, induced deletion of Gli1 is sufficient to drive minifascicle formation. Thus, Gli1 regulates the development and is required to maintain the endoneurial architecture of peripheral nerves. SIGNIFICANCE STATEMENTPeripheral nerves are organized into distinct cellular/ECM compartments: the epineurium, perineurium and endoneurium. This organization, with its associated cellular constituents, are critical for the structural and metabolic support of nerves and their response to injury. Here, we show Gli1 - a transcription factor normally expressed downstream of hedgehog signaling - is required for the proper organization of the endoneurium but not the perineurium. Unexpectedly, Gli1 expression by endoneurial cells is independent of, and functions non-redundantly with, Schwann Cell-derived Desert Hedgehog in regulating peripheral nerve architecture. These results further delineate how peripheral nerves acquire their distinctive organization during normal development and highlight mechanisms that may regulate their reorganization in pathologic settings including peripheral neuropathies and nerve injury.

neuroscience↗

bioRxiv2021

Gpnmb inhibits oligodendrocyte differentiation of adult neural stem cells by amplifying TGFβ1 signaling

Gli1 expressing neural stem cells, in the subventricular zone of the adult mammalian brain, respond to demyelination injury by differentiating into oligodendrocytes. We have identified Gpnmb as a novel regulator of oligodendrogenesis in Gli1 neural stem cells, whose expression is induced by TGF{beta}1 signaling via Gli1, in response to a demyelinating injury. Upregulation of Gpnmb further activates the TGF{beta}1 pathway by increasing the expression of the TGF{beta}1 binding receptor subunit, TGF{beta}R2. Thus the TGF{beta}1[->]Gli1[->]Gpnmb[->]TGF{beta}R2 signaling pathway forms a feed forward loop for sustained activation of TGF{beta}1 signaling in Gli1 neural stem cells, resulting in inhibition of their differentiation into mature oligodendrocytes following demyelination.

neuroscience↗

bioRxiv2021

Transcriptomic analysis of loss of Gli1 in neural stem cells responding to demyelination in the mouse brain

In the adult mammalian brain, Gli1 expressing neural stem cells reside in the subventricular zone and their progeny are recruited to sites of demyelination in the white matter where they generate new oligodendrocytes, the myelin forming cells. Remarkably, genetic loss or pharmacologic inhibition of Gli1 enhances the efficacy of remyelination by these neural stem cells. To understand the molecular mechanisms involved, we performed a transcriptomic analysis of this Gli1-pool of neural stem cells. We compared murine NSCs with either intact or deficient Gli1 expression from adult mice on a control diet or on a cuprizone diet which induces widespread demyelination. These data will be a valuable resource for identifying therapeutic targets for enhancing remyelination in demyelinating diseases like multiple sclerosis.

neuroscience↗

bioRxiv2019

Gli2 is necessary for migration of ventral Neural Stem Cells to demyelinated lesions

Enhancing repair of myelin is an important therapeutic goal in many neurological disorders characterized by demyelination. In the healthy adult brain, ventral neural stem cells in the sub-ventricular zone are marked by Gli1 expression and do not generate oligodendrocytes. However, in response to demyelination they migrate to lesions and differentiate into oligodendrocytes. Inhibition of Gli1 further increases their contribution to remyelination. Gli1 and Gli2 are both transcriptional effectors of the Sonic Hedgehog pathway with highly conserved domains but the role of Gli2 in remyelination by ventral neural stem cells is not clear. Here we show that while genetic ablation of Gli1 in the ventral neural stem cells increases remyelination, loss of Gli2 in these cells decreases their migration to the white matter lesion and reduces their differentiation into mature oligodendrocytes. These studies indicate Gli1 and Gli2 have distinct, non-redundant functions in NSCs, including that Gli2 is essential for the enhanced remyelination mediated by Gli1 inhibition. They highlight the importance of designing specific Gli1 inhibitors that do not inhibit Gli2 as a strategy for therapies targeting the Shh pathway.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC=\"FIGDIR/small/668418v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (36K):\norg.highwire.dtl.DTLVardef@177fa0aorg.highwire.dtl.DTLVardef@1c0a954org.highwire.dtl.DTLVardef@1accdc5org.highwire.dtl.DTLVardef@1f97eeb_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗