DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration

Sarkar, Souradeep R.; Dubey, Vinay Kumar; Jahagirdar, A.P.; Lakshmanan, Vairavan; Haroon, Mohamed Mohamed; Sowndarya, Sai; Sowdhamini, Ramanathan; Palakodeti, Dasaradhi

doi:10.1016/j.ydbio.2022.04.011

Cited by 6 publications

(4 citation statements)

References 88 publications

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“…These time points were selected to capture major events during Hofstenia regeneration, including the wound response (6 hpa), completion of wound healing and polarity determination (24 hpa), blastema formation (72 hpa), and the return of most major structures during regeneration such as the brain (8 dpa) 22 , 42 , 46 , 49 . 8 dpa is the typical end-point of regeneration assays in acoels and planarians 42 , 50 – 53 , and we added the later 17 dpa and 29 dpa time points, to ask if these data would recover a signature for the “end” of regeneration. In other words, to see if gene expression would return to steady state a month after amputation.…”

Section: Resultsmentioning

confidence: 99%

Acoel single-cell atlas reveals expression dynamics and heterogeneity of adult pluripotent stem cells

et al. 2023

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Adult pluripotent stem cell (aPSC) populations underlie whole-body regeneration in many distantly-related animal lineages, but how the underlying cellular and molecular mechanisms compare across species is unknown. Here, we apply single-cell RNA sequencing to profile transcriptional cell states of the acoel worm Hofstenia miamia during postembryonic development and regeneration. We identify cell types shared across stages and their associated gene expression dynamics during regeneration. Functional studies confirm that the aPSCs, also known as neoblasts, are the source of differentiated cells and reveal transcription factors needed for differentiation. Subclustering of neoblasts recovers transcriptionally distinct subpopulations, the majority of which are likely specialized to differentiated lineages. One neoblast subset, showing enriched expression of the histone variant H3.3, appears to lack specialization. Altogether, the cell states identified in this study facilitate comparisons to other species and enable future studies of stem cell fate potentials.

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Section: Resultsmentioning

confidence: 99%

Acoel single-cell atlas reveals expression dynamics and heterogeneity of adult pluripotent stem cells

et al. 2023

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“…Body wall musculature has been implicated in providing positional information to pattern different tissues in the body ( 11 , 44 , 55 ). Even though the patterning along the AP axis was defective in pak1(RNAi) animals, we did not observe any gross abnormalities in body wall musculature as visualized by 6G10-2C7 antibody ( 56 ).…”

Section: Resultsmentioning

confidence: 99%

A PAK family kinase and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration

Doddihal,

Mann,

Ross

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Successful regeneration of missing tissues requires seamless integration of positional information along the body axes. Planarians, which regenerate from almost any injury, use conserved, developmentally important signaling pathways to pattern the body axes. However, the molecular mechanisms which facilitate cross talk between these signaling pathways to integrate positional information remain poorly understood. Here, we report a p21-activated kinase ( smed-pak1 ) which functionally integrates the anterior–posterior (AP) and the medio-lateral (ML) axes. pak1 inhibits WNT/β-catenin signaling along the AP axis and, functions synergistically with the β-catenin-independent WNT signaling of the ML axis. Furthermore, this functional integration is dependent on warts and merlin —the components of the Hippo/Yorkie (YKI) pathway. Hippo/YKI pathway is a critical regulator of body size in flies and mice, but our data suggest the pathway regulates body axes patterning in planarians. Our study provides a signaling network integrating positional information which can mediate coordinated growth and patterning during planarian regeneration.

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“…For DDX24, a correlation has been shown between its elevated levels in hepatocellular carcinoma tissues and poor prognosis of this disease [ 47 ]. Interestingly, DDX24 is necessary for the organization of muscle fibers and specification of the anterior pole, which is important for regenerating the head in planarians [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

Insights into the Cellular Localization and Functional Properties of TSPYL5 Protein

Silonov,

Smirnov,

Shmidt

et al. 2023

IJMS

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In recent years, the role of liquid–liquid phase separation (LLPS) and intrinsically disordered proteins (IDPs) in cellular molecular processes has received increasing attention from researchers. One such intrinsically disordered protein is TSPYL5, considered both as a marker and a potential therapeutic target for various oncological diseases. However, the role of TSPYL5 in intracellular processes remains unknown, and there is no clarity even in its intracellular localization. In this study, we characterized the intracellular localization and exchange dynamics with intracellular contents of TSPYL5 and its parts, utilizing TSPYL5 fusion proteins with EGFP. Our findings reveal that TSPYL5 can be localized in both the cytoplasm and nucleoplasm, including the nucleolus. The nuclear (nucleolar) localization of TSPYL5 is mediated by the nuclear/nucleolar localization sequences (NLS/NoLS) identified in the N-terminal intrinsically disordered region (4–27 aa), while its cytoplasmic localization is regulated by the ordered NAP-like domain (198–382 aa). Furthermore, our results underscore the significant role of the TSPYL5 N-terminal disordered region (1–198 aa) in the exchange dynamics with the nucleoplasm and its potential ability for phase separation. Bioinformatics analysis of the TSPYL5 interactome indicates its potential function as a histone and ribosomal protein chaperone. Taken together, these findings suggest a significant contribution of liquid–liquid phase separation to the processes involving TSPYL5, providing new insights into the role of this protein in the cell’s molecular life.

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DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration

Cited by 6 publications

References 88 publications

Acoel single-cell atlas reveals expression dynamics and heterogeneity of adult pluripotent stem cells

Acoel single-cell atlas reveals expression dynamics and heterogeneity of adult pluripotent stem cells

A PAK family kinase and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration

Insights into the Cellular Localization and Functional Properties of TSPYL5 Protein

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