Roles of Notch signalling in early embryonic development

Metazoan embryonic development requires a complex interplay of morphological processes coordinated with self-renewal and differentiation to correctly specify and maintain body cell types in the correct location. Notch signalling is a metazoan specific arbiter of cell fate decision processes, known to control lateral inhibition and asymmetric cell division processes throughout the metazoa and in the development of all metazoan organs.

In this thesis, we study the effects of Notch signalling on early embryonic development using mouse embryonic stem (ES) cells as an in vitro model system. We determine that Notch signalling is able to crosstalk with hypoxic signalling on the transcriptome level though the majority of gene regulation by either pathway is independent of the other. Secondly, we show that Notch signalling is required for temporal activation of CyclinD1 expression at day 3 of ES cell neural differentiation. Finally we show that Notch signalling is required for specification of Radial Glial Cell (RGC) types ES cell derived neural rosettes and that the maintenance of RGCs is required for neural epithelial polarity.

These data corroborate that canonical Notch signalling is not required in mouse for embryonic processes prior to neural epithelial formation but that it is required for structural morphology in the nervous system.

List of scientific papers

I. Interactions between Notch- and hypoxia-induced transcriptomes in embryonic stem cells. Main H, Lee KL, Yang H, Haapa-Paananen S, Edgren H, Jin S, Sahlgren C, Kallioniemi O, Poellinger L, Lim B, Lendahl U. Exp Cell Res. 2010 May 15; 316 (9): 1610-24.
https://doi.org/10.1016/j.yexcr.2009.12.012

II. Notch induces CyclinD1-dependent proliferation during a specific temporal window of neural differentiation in ES cells. Das D, Lanner F, Main H, Andersson ER, Bergmann O, Sahlgren C, Heldring N, Hermanson O, Hansson EM, Lendahl U. Dev Biol. 2010 Dec 15; 348(2): 153-66.
https://doi.org/10.1016/j.ydbio.2010.09.018

III. Regulation of apical/basal cell polarity by Notch during neural differentiation. Heather Main, Emma R. Andersson and Urban Lendahl. [Manuscript]