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Advisor(s)
Abstract(s)
Background: Mammalian early embryo development requires a well-orchestrated interplay of cell signaling
pathways. Notch is a major regulatory pathway involved in cell-fate determination in embryonic and adult
scenarios. However, the role of Notch in embryonic pre-implantation development is controversial. In particular,
Notch role on blastocyst development and hatching remains elusive, and a complete picture of the transcription
and expression patterns of Notch components during this time-period is not available.
Results: This study provided a comprehensive view on the dynamics of individual embryo gene transcription and
protein expression patterns of Notch components (receptors Notch1–4; ligands Dll1 and Dll4, Jagged1–2; and
effectors Hes1–2), and their relationship with transcription of gene markers of pluripotency and differentiation (Sox2,
Oct4, Klf4, Cdx2) during mouse blastocyst development and hatching. Transcription of Notch1–2, Jagged1–2 and
Hes1 was highly prevalent and dynamic along stages of development, whereas transcription of Notch3–4, Dll4 and
Hes2 had a low prevalence among embryos. Transcription levels of Notch1, Notch2, Jagged2 and Hes1 correlated
with each other and with those of pluripotency and differentiation genes. Gene transcription was associated to
protein expression, except for Jagged2, where high transcription levels in all embryos were not translated into
protein. Presence of Notch signaling activity was confirmed through nuclear NICD and Hes1 detection, and
downregulation of Hes1 transcription following canonical signaling blockade with DAPT. In vitro embryo culture
supplementation with Jagged1 had no effect on embryo developmental kinetics. In contrast, supplementation with
Jagged2 abolished Jagged1 transcription, downregulated Cdx2 transcription and inhibited blastocyst hatching.
Notch signaling blockade by DAPT downregulated transcription of Sox2, and retarded embryo hatching.
Conclusion: Transcription of Notch genes showed a dynamic pattern along blastocyst development and hatching.
Data confirmed Notch signaling activity, and lead to the suggestion that Notch canonical signaling may be
operating through Notch1, Notch3, Jagged1 and Hes1. Embryo culture supplementation with Jagged1 and
Jagged2 unveiled a possible regulatory effect between Jagged1, Cdx2 and blastocyst hatching. Overall, results
indicate that a deregulation in Notch signaling, either by its over or under-activation, affects blastocyst
development and hatching.
Description
Research Areas: Developmental Biology
Keywords
Blastocyst Development Hatching Notch Mouse
Pedagogical Context
Citation
Batista MR, Diniz P, Torres A, Murta D, Lopes-da-Costa L, Silva E. 2020. Notch signaling in mouse blastocyst development and hatching, BMC Developmental Biology, 20(1):9. Doi 10.1186/s12861-020-00216-2
Publisher
BMC