@article {2242, title = {Mechanical instability of adherens junctions overrides intrinsic quiescence of hair follicle stem cells.}, journal = {Dev Cell}, volume = {56}, year = {2021}, month = {2021 Mar 22}, pages = {761-780.e7}, abstract = {

Vinculin, a mechanotransducer associated with both adherens junctions (AJs) and focal adhesions (FAs), plays a central role in force transmission through cell-cell and cell-substratum contacts. We generated the conditional knockout (cKO) of vinculin in murine skin that results in the loss of bulge stem cell (BuSC) quiescence and promotes continual cycling of the hair follicles. Surprisingly, we find that the AJs in vinculin cKO cells are mechanically weak and impaired in force generation despite increased junctional expression of E-cadherin and α-catenin. Mechanistically, we demonstrate that vinculin functions by keeping α-catenin in a stretched/open conformation, which in turn regulates the retention of YAP1, another potent mechanotransducer and regulator of cell proliferation, at the AJs. Altogether, our data provide mechanistic insights into the hitherto-unexplored regulatory link between the mechanical stability of cell junctions and contact-inhibition-mediated maintenance of BuSC quiescence.

}, issn = {1878-1551}, doi = {10.1016/j.devcel.2021.02.020}, author = {Biswas, Ritusree and Banerjee, Avinanda and Lembo, Sergio and Zhao, Zhihai and Lakshmanan, Vairavan and Lim, Ryan and Le, Shimin and Nakasaki, Manando and Kutyavin, Vassily and Wright, Graham and Palakodeti, Dasaradhi and Ross, Robert S and Jamora, Colin and Vasioukhin, Valeri and Jie, Yan and Raghavan, Srikala} } @article {2274, title = {Mitochondrial state determines functionally divergent stem cell population in planaria.}, journal = {Stem Cell Reports}, volume = {16}, year = {2021}, month = {2021 May 11}, pages = {1302-1316}, abstract = {

Mitochondrial state changes were shown to be critical for stem cell function. However, variation in the mitochondrial content in stem cells and the implication, if any, on differentiation is poorly understood. Here, using cellular and molecular studies, we show that the planarian pluripotent stem cells (PSCs) have low mitochondrial mass compared with their progenitors. Transplantation experiments provided functional validation that neoblasts with low mitochondrial mass are the true PSCs. Further, the mitochondrial mass correlated with OxPhos and inhibiting the transition to OxPhos dependent metabolism in cultured cells resulted in higher PSCs. In summary, we show that low mitochondrial mass is a hallmark of PSCs in planaria and provide a mechanism to isolate live, functionally active, PSCs from different cell cycle stages (G0/G1 and S, G2/M). Our study demonstrates that the change in mitochondrial metabolism, a feature of PSCs is conserved in planaria and highlights its role in organismal regeneration.

}, issn = {2213-6711}, doi = {10.1016/j.stemcr.2021.03.022}, author = {Mohamed Haroon, Mohamed and Lakshmanan, Vairavan and Sarkar, Souradeep R and Lei, Kai and Vemula, Praveen Kumar and Palakodeti, Dasaradhi} } @article {2109, title = {Modulation of β-catenin levels regulates cranial neural crest patterning and dispersal into first pharyngeal arch.}, journal = {Dev Dyn}, year = {2020}, month = {2020 May 19}, abstract = {

BACKGROUND: Vertebrate cranial neural crest cells (CNCCs) are multipotent, proximal to the source CNCC form the cranial ganglia. Distally, in the pharyngeal arches, they give rise to the craniofacial skeleton and connective tissues. Fate choices are made as CNCC pattern into distinct destination compartments. In spite of this importance, the mechanism patterning CNCC is poorly defined.

RESULTS: Here, we report that a novel β-catenin-dependent regulation of N-Cadherin levels may drive CNCC patterning. In mouse embryos, at the first pharyngeal arch axial level, membrane β-catenin levels correlate with the extent of N-cadherin-mediated adhesion and thus suggest the presence of collective and dispersed states of CNCC. Using in vitro human neural crest model and chemical modulators of β-catenin levels, we show a requirement for down-modulating β-catenin for regulating N-cadherin levels and cell-cell adhesion. Similarly, in β-catenin gain-of-function mutant mouse embryos, CNCC fail to lower N-cadherin levels. This indicates a failure to reduce cell-cell adhesion, which may underlie the failure of mutant CNCC to populate first pharyngeal arch.

CONCLUSION: We suggest that β-catenin-mediated regulation of CNCC adhesion, a previously underappreciated mechanism, underlies the patterning of CNCC into fate-specific compartments.

}, issn = {1097-0177}, doi = {10.1002/dvdy.208}, author = {Javali, Alok and Lakshmanan, Vairavan and Palakodeti, Dasaradhi and Sambasivan, Ramkumar} } @article {1199, title = {The miR-124 family of microRNAs is crucial for regeneration of the brain and visual system in the planarian Schmidtea mediterranea}, journal = {Development}, volume = {144}, year = {2017}, pages = {3211{\textendash}3223}, abstract = {

Brain regeneration in planarians is mediated by precise spatiotemporal control of gene expression and is crucial for multiple aspects of neurogenesis. However, the mechanisms underpinning the gene regulation essential for brain regeneration are largely unknown. Here, we investigated the role of the miR-124 family of microRNAs in planarian brain regeneration. The miR-124 family (miR-124) is highly conserved in animals and regulates neurogenesis by facilitating neural differentiation, yet its role in neural wiring and brain organization is not known. We developed a novel method for delivering anti-miRs using liposomes for the functional knockdown of microRNAs. Smed-miR-124 knockdown revealed a key role for these microRNAs in neuronal organization during planarian brain regeneration. Our results also demonstrated an essential role for miR-124 in the generation of eye progenitors. Additionally, miR-124 regulates Smed-slit-1, which encodes an axon guidance protein, either by targeting slit-1 mRNA or, potentially, by modulating the canonical Notch pathway. Together, our results reveal a role for miR-124 in regulating the regeneration of a functional brain and visual system.

}, issn = {0950-1991}, doi = {10.1242/dev.144758}, url = {http://dev.biologists.org/content/144/18/3211}, author = {Sasidharan, Vidyanand and Marepally, Srujan and Elliott, Sarah A. and Baid, Srishti and Lakshmanan, Vairavan and Nayyar, Nishtha and Bansal, Dhiru and S{\'a}nchez Alvarado, Alejandro and Vemula, Praveen Kumar and Palakodeti, Dasaradhi} }