Extended Data Fig. 4: Elevated BCL-XL expression in early embryonic epidermis is sufficient to block Mycn-dependent apoptotic cell competition and has no long-term consequence for skin development. | Nature

Extended Data Fig. 4: Elevated BCL-XL expression in early embryonic epidermis is sufficient to block Mycn-dependent apoptotic cell competition and has no long-term consequence for skin development.

From: Distinct modes of cell competition shape mammalian tissue morphogenesis

Extended Data Fig. 4

a, Doxycycline-inducible activation of K14rtTA by lentivirally delivered TRE-driven transgenes at E12.5 (embryo transduced with TRE-GFP is shown, representative of results obtained in two independent litters). b, Experimental strategy for elevating BCL-XL expression in the early embryonic epidermis. TRE-Bcl2l1 was transduced at a relatively high titre, whereas CreRFP was transduced at a low titre (n = 4 embryos). c, Whole-mount images of E12.5 transduced embryos show that >50% of basal epidermal cells express BCL-XL and surround a small population of cells that express both BCL-XL (green) and CreRFP (red). TUNEL (white, signal inverted in right-most image) was quantified (Fig. 2a) relative to the position of CreRFP-expressing Mycn+/– loser cells that also express BCL-XL. Note that appreciable TUNEL labelling was not observed. Images are representative of data obtained from two litters. d, Proliferation in WT embryos at E12.5 (n = 4 per genotype) was lower in BCL-XL+ cells than in controls. At E17.5 there was no difference in proliferation between controls (n = 11) and BCL-XL+ cells (n = 14; n denotes number of images analysed from embryos from two litters for each genotype; two-sided Mann–Whitney test). e, Induction of BCL-XL expression from E9.5 to E15.5 had no appreciable consequence for epidermal differentiation or thickness at E17.5 (control n = 54; BCL-XL+ n = 68; n denotes number of thickness measurements taken from images of back skin cryosections from two mice per genotype). Representative images of back skin sections are shown immunolabelled for K14 (green) to mark the basal epidermis, and K10, Loricrin, or Filaggrin (red) to mark the differentiating spinous and granular layers. Dashed lines denote epidermal–dermal border; solid line demarcates the skin surface. Scale bars, 50 μm. Data are mean ± s.e.m.

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