Xenopus embryos show a compensatory response following perturbation of the Notch signaling pathway
Abstract
As an essential feature of development, robustness ensures that embryos attain a consistent phenotype despite genetic and environmental variation. The growing number of examples demonstrating that embryos can mount a compensatory response to germline mutations in key developmental genes has heightened interest in the phenomenon of embryonic robustness. While considerable progress has been made in elucidating genetic compensation in response to germline mutations, the diversity, mechanisms, and limitations of embryonic robustness remain unclear. In this work, we have examined whether Xenopus laevis embryos are able to compensate for perturbations of the Notch signaling pathway induced by RNA injection constructs that either upregulate or inhibit this signaling pathway. Consistent with earlier studies, we found that at neurula stages, hyperactivation of the Notch pathway inhibited neural differentiation while inhibition of Notch signaling increases premature differentiation as assayed by neural beta tubulin expression. However, surprisingly, by hatching stages, embryos begin to compensate for these perturbations, and by swimming tadpole stages most embryos exhibited normal neuronal gene expression. Using cell proliferation and TUNEL assays, we show that the compensatory response is, in part, mediated by modulating levels of cell proliferation and apoptosis. This work provides an additional model for addressing the mechanisms of embryonic robustness and of genetic compensation.
Additional Information
© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Received 24 July 2019, Revised 3 December 2019, Accepted 24 December 2019, Available online 30 December 2019. This work was supported by National Institutes of Health grant 1 R15 HD096415-01 and National Science Foundation grant IOS 1257895 to MSS. We thank Ronnie Cutler and colleagues at Society for Developmental Biology meetings for valuable discussions at our poster and oral presentations. Declaration of competing interest: None.Attached Files
Published - 1-s2.0-S0012160619304476-main.pdf
Accepted Version - nihms-1584297.pdf
Files
Name | Size | Download all |
---|---|---|
md5:1c3c26960523f94d5ae43fb1b6b5a1f0
|
2.3 MB | Preview Download |
md5:9fd7a9045069404b4e532db76d339e98
|
1.6 MB | Preview Download |
Additional details
- PMCID
- PMC7263880
- Eprint ID
- 103059
- Resolver ID
- CaltechAUTHORS:20200507-081319062
- 1 R15 HD096415-01
- NIH
- IOS-1257895
- NSF
- Created
-
2020-05-07Created from EPrint's datestamp field
- Updated
-
2022-02-15Created from EPrint's last_modified field