The roles of Bcl-xL in modulating apoptosis during development of Xenopus laevis

Johnston, Jillian; Chan, Robert K W; Calderón-Segura, María Elena; McFarlane, Sarah; Browder, Leon W.

doi:10.1186/1471-213x-5-20

Cited by 11 publications

(10 citation statements)

References 55 publications

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“…Our previous study also showed that M50054 treatment from st. 27 to st. 34/35 did not induce eye defects (Kha et al, 2018). These data were also consistent with a previous study showing that overexpression of the anti-apoptotic gene, BcL-xL, during embryogenesis did not induce eye defects (Johnston et al, 2005). Thus, apoptosis does not appear to be required for eye development.…”

Section: Resultssupporting

confidence: 93%

Using the Xenopus Developmental Eye Regrowth System to Distinguish the Role of Developmental Versus Regenerative Mechanisms

2019

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A longstanding challenge in regeneration biology is to understand the role of developmental mechanisms in restoring lost or damaged tissues and organs. As these body structures were built during embryogenesis, it is not surprising that a number of developmental mechanisms are also active during regeneration. However, it remains unclear whether developmental mechanisms act similarly or differently during regeneration as compared to development. Since regeneration is studied in the context of mature, differentiated tissues, it is difficult to evaluate comparative studies with developmental processes due to the latter’s highly proliferative environment. We have taken a more direct approach to study regeneration in a developmental context (regrowth). Xenopus laevis , the African clawed frog, is a well-established model for both embryology and regeneration studies, especially for the eye. Xenopus eye development is well-defined. Xenopus is also an established model for retinal and lens regeneration studies. Previously, we demonstrated that Xenopus tailbud embryo can successfully regrow a functional eye that is morphologically indistinguishable from an age-matched control eye. In this study, we assessed the temporal regulation of retinal differentiation and patterning restoration during eye regrowth. Our findings showed that during regrowth, cellular patterning and retinal layer formation was delayed by approximately 1 day but was restored by 3 days when compared to eye development. An assessment of the differentiation of ganglion cells, photoreceptor cells, and Müller glia indicated that the retinal birth order generated during regrowth was consistent with that observed for eye development. Thus, retina differentiation and patterning during regrowth is similar to endogenous eye development. We used this eye regrowth model to assess the role of known mechanisms in development versus regrowth. Loss-of-function studies showed that Pax6 was required for both eye development and regrowth whereas apoptosis was only required for regrowth. Together, these results revealed that the mechanisms required for both development and regrowth can be distinguished from regrowth-specific ones. Our study highlights this developmental model of eye regrowth as a robust platform to systematically and efficiently define the molecular mechanisms that are required for regeneration versus development.

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Section: Resultssupporting

confidence: 93%

Using the Xenopus Developmental Eye Regrowth System to Distinguish the Role of Developmental Versus Regenerative Mechanisms

2019

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“…S5D,E). In agreement with the notion that apoptosis was not involved in FGF-mediated specification of lateral GRP cells, injection of the anti-apoptotic B-cell CLL/lymphoma (bcl-XL) DNA construct, which inhibits chemically induced apoptosis (Johnston et al, 2005), into the lineage of the lateral GRP was unable to rescue SU5402-induced loss of nodal1/dand5positive GRP cells ( Fig. S5F-K).…”

Section: Fgf Signaling During Gastrulation Is Necessary For Lr Asymmetrysupporting

confidence: 83%

“…The apoptosis rescue experiment using Bcl-XL was performed by targeting 8 pg of Bcl-XL/CS2+ plasmid DNA (Johnston et al, 2005) into the left and right somitic GRP lineages (dorsolateral part of the 4-cell embryo). Embryos were treated with either DMSO or 60 µM SU5402 from stage 12-17, fixed and processed for in situ hybridization (ISH) using dand5-and nodal1-specific antisense probes.…”

Section: Analysis Of Apoptosis By Tunel Staining and Bcl-xl Injectionsmentioning

confidence: 99%

A dual function of FGF signaling in Xenopus left-right axis formation

et al. 2019

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Organ left-right (LR) asymmetry is a conserved vertebrate feature, which is regulated by left-sided activation of Nodal signaling. Nodal asymmetry is established by a leftward fluid-flow generated at the ciliated LR organizer (LRO). Although the role of fibroblast growth factor (FGF) signaling pathways during mesoderm development is conserved, diverging results from different model organisms suggest a non-conserved function in LR asymmetry. Here, we demonstrate that FGF is required during gastrulation in a dual function at consecutive stages of Xenopus embryonic development. In the early gastrula, FGF is necessary for LRO precursor induction, acting in parallel with FGF-mediated mesoderm induction. During late gastrulation, the FGF/Ca 2+-branch is required for specification of the flow-sensing lateral LRO cells, a function related to FGF-mediated mesoderm morphogenesis. This second function in addition requires input from the calcium channel Polycystin-2. Thus, analogous to mesoderm development, FGF activity is required in a dual role for laterality specification; namely, for generating and sensing leftward flow. Moreover, our findings in Xenopus demonstrate that FGF functions in LR development share more conserved features across vertebrate species than previously anticipated.

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“…Proteins-Five members of the Xenopus Bcl-2 family of proteins (xBcl-w/xR1, xBcl-x L /xR11, xBax, xBid, and xBok) were functionally characterized in the previous studies (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In addition, partial or complete nucleotide sequences of 10 Bcl-2 family proteins (xBcl-2, xBcl-B, xBcl-G, xBcl2L12, xBcl2L13, xMcl-1, xBak, xBim, xBmf, and xNoxa) were deposited in the Xenopus nucleotide database, but the functions of their protein products remained uncharacterized (42)(43)(44).…”

Section: Identification and Rt-pcr Analysis Of Xenopus Bcl-2 Familymentioning

confidence: 99%

“…They are classified as either anti-apoptotic or pro-apoptotic, and the functional balance between these two groups controls the mitochondria-mediated intrinsic pathway of apoptosis. Although more than 10 members of the Bcl-2 family of proteins have been identified in Xenopus laevis (simply referred to as Xenopus hereafter), their functional characterizations are not yet complete (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

Anti-apoptotic Activity and Proteasome-mediated Degradation of Xenopus Mcl-1 Protein in Egg Extracts

Tsuchiya

Yamashita

2011

Journal of Biological Chemistry

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Xenopus egg extracts execute spontaneous apoptosis without the requirement of transcription and translation, and this intrinsic mechanism is supposed to be involved in the physiological elimination of aged eggs. Although apoptosis in this system is carried out by maternally stockpiled materials, the endogenous apoptosis regulators present in egg extracts are still poorly characterized. Here we examined the mRNA expression profiles and apoptosis-regulating functions of 13 Xenopus Bcl-2 family proteins in egg extracts. Among these, we found that endogenous Xenopus Mcl-1 (xMcl-1) physiologically inhibited apoptosis by counteracting the pro-apoptotic activity of endogenous Xenopus Bid in egg extracts. Exogenously added recombinant xMcl-1 was rapidly degraded by proteasome in egg extracts, and we identified the destabilizing region in the N terminus of xMcl-1. Our results suggest that the proteolytic decay of xMcl-1 may change the functional balance between pro-and anti-apoptotic activities of Bcl-2 family proteins, thereby regulating the timing of cytochrome c release in egg extracts.

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The roles of Bcl-xL in modulating apoptosis during development of Xenopus laevis

Cited by 11 publications

References 55 publications

Using the Xenopus Developmental Eye Regrowth System to Distinguish the Role of Developmental Versus Regenerative Mechanisms

Using the Xenopus Developmental Eye Regrowth System to Distinguish the Role of Developmental Versus Regenerative Mechanisms

A dual function of FGF signaling in Xenopus left-right axis formation

Anti-apoptotic Activity and Proteasome-mediated Degradation of Xenopus Mcl-1 Protein in Egg Extracts

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