Biology subjects

Otgonbaatar, A.

Publications and source records attributed to Otgonbaatar, A..

2 recordsLinked to original sources

bioRxiv2026

Junctional β-Catenin Stabilization Links Wnt Signaling and Force Generation

{beta}-catenin plays two fundamental roles in animal tissues: it acts as a transcriptional effector of canonical Wnt signaling and as a core structural component of adherens junctions that mediate cell-cell adhesion. In canonical Wnt signaling, the post-transcriptional regulation of {beta}-catenin abundance, primarily through regulated phosphorylation, ubiquitination, and proteasomal degradation, determines whether the pathway is "off" or "on." Despite the central importance of {beta}-catenin stabilization, in vivo measurements of {beta}-catenin protein lifetime and stabilization dynamics during development remain limited. Here, we measure the stability of endogenous {beta}-catenin in vivo using tandem fluorescent protein timers (tFPs; "Timers") inserted as minimally disruptive cassettes within the endogenous locus. Timers allow simultaneous visualization of a newly synthesized, rapidly accumulating pool (fast-maturing GFP) and a long-lived, stabilized pool (slow-maturing RFP). Surprisingly, the strongest stabilization does not occur in canonical Wnt patterning stripes; instead, we observe marked stabilization of junctional {beta}-catenin at the leading edge during dorsal closure, a force-generating morphogenetic process. This stabilization is not explained by canonical Wnt ligand input and seems to reflect a stability program linked to {beta}-catenins adhesive function in adherens junctions. We suggest that a stable junctional pool of {beta}-catenin is vital for dorsal closure mechanics and provide evidence that this stabilization is regulated by Dishevelled and JNK, thus connecting Wnt pathway components to mechanotransduction.

developmental biology↗

bioRxiv2022

Combining Stem Cell Rejuvenation and Senescence Targeting to Synergistically Extend Lifespan

Why biological age is a major risk factor for many of the most important human diseases remains mysterious. We know that as organisms age, stem cell pools are exhausted while senescent cells progressively accumulate. Independently, induction of pluripotency via expression of Yamanaka factors (Oct4, Klf4, Sox2, c-Myc; OKSM) and clearance of senescent cells have each been shown to ameliorate cellular and physiological aspects of aging, suggesting that both processes are drivers of organismal aging. However, stem cell exhaustion and cellular senescence likely interact in the etiology and progression of age-dependent diseases because both undermine tissue and organ homeostasis in different if not complementary ways. Here, we combine transient cellular reprogramming (stem cell rejuvenation) with targeted removal of senescent cells to test the hypothesis that simultaneously targeting both cell-fate based aging mechanisms will maximize life and health span benefits. We show that these interventions protect the intestinal stem cell pool, lower inflammation, activate pro-stem cell signaling pathways, and synergistically improve health and lifespan. Our findings suggest that a combination therapy, simultaneously replacing lost stem cells and removing senescent cells, shows synergistic potential for anti-aging treatments. Our finding that transient expression of both is the most effective suggests that drug-based treatments in non-genetically tractable organisms will likely be the most translatable.

developmental biology↗