Fig. 4: Gamma secretase inhibitor DAPT reverses neurogenesis and neurite outgrowth defects in MELAS organoids. | Cell Death & Disease

Fig. 4: Gamma secretase inhibitor DAPT reverses neurogenesis and neurite outgrowth defects in MELAS organoids.

From: Organoid cultures of MELAS neural cells reveal hyperactive Notch signaling that impacts neurodevelopment

Fig. 4

a qPCR analysis of Notch effector genes HES1 and HEY1 indicating that DAPT treatment inhibits Notch signaling. b MELAS organoids were treated with DMSO or DAPT from days 18 to 28, and immunostaining of OLIG2 and ISL1 was performed at either day 28 or day 35. In the presence of DAPT, the OLIG2 motor neuron progenitor population is reduced while ISL1+ motor neuron population is increased. c Immunostaining of cryosectioned organoids derived from MELAS iPSCs revealed changes in the cyto-architecture after DAPT treatment. d Day 21 organoids were seeded onto Matrigel-coated plates and allowed to attach and extend their neurites for 7 days. On day 28, cultures were fixed and immunostaining for motor neuron axon marker SMI-32 was performed. Neurite lengths were then measured using ImageJ. Scale bars indicate 100 μm. ***p-value < 0.001.

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