... supporting cells were transformed into IHCs by ectopically expressing Atoh1 transiently and Tbx2 permanently. Notably, the new IHCs expressed the functional marker vGlut3 and presented similar transcriptomic and electrophysiological properties to wild-type IHCs. Furthermore, the formation efficiency...

...; this avoids mouse breeding and serves as a rapid screening approach for nonlethal genes. However, loss of function of 25% of mammalian genes causes early lethality. Here, we induced CRISPR-stop in one of the two blastomeres of the zygote, a method we name mosaic CRISPR-stop, to produce mosaic Atoh1 and Sox10...

... of cochlear formation including cell fate, outgrowth and patterning. Atoh1 Deafness Hearing Notch Organ of Corti Radial intercalation The mammalian inner ear is a remarkable structure, made up of a labyrinth of elaborate ducts and canals ( Fig. 1 ). Together, these facilitate the perception...

... rows of outer HCs (OHCs) are organized is not well understood. Here, we investigated the process of HC induction by monitoring Atoh1 expression in cochlear explants of Atoh1- EGFP knock-in mouse embryos and showed that only the cells that express Atoh1 over a certain threshold are selected for HC fate...

...Yassan Abdolazimi; Zlatka Stojanova; Neil Segil Determination of cell fate within the prosensory domain of the developing cochlear duct relies on the temporal and spatial regulation of the bHLH transcription factor Atoh1 . Auditory hair cells and supporting cells arise in a wave of differentiation...

... and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse...

... Summary: This Review compares the mechanisms at play during inner ear hair cell development and regeneration, highlighting gaps in our knowledge and proposing future directions in research and therapeutics. Wnt FGF Shh Notch Atoh1 p27 Kip1 , Cdkn1b Like supporting cells, hair cells...

... interests The authors declare no competing financial interests. © 2014. Published by The Company of Biologists Ltd 2014 Granule cell Atoh1 Autistic spectrum disorder Medulloblastoma Ptf1a Purkinje cell The cerebellum (‘little brain’) resides at the anterior end of the hindbrain...

...Thomas Butts; Michalina Hanzel; Richard J. T. Wingate The cerebellum has evolved elaborate foliation in the amniote lineage as a consequence of extensive Atoh1 -mediated transit amplification in an external germinal layer (EGL) comprising granule cell precursors. To explore the evolutionary origin...

... robust. The model suggests that autoactivation of proneural factor Atoh1, upstream of Dl1, is a fundamental component for robustness. The results stress the importance of the levels of Notch signaling and ligand competition for Notch function. * Present address: The Buck Institute, 8001 Redwood...

...% of the population. Here, we developed two genetic strategies to ablate neonatal mouse cochlear hair cells in vivo . Both Pou4f3 DTR/+ and Atoh1-CreER™; ROSA26 DTA/+ alleles allowed selective and inducible hair cell ablation. After hair cell loss was induced at birth, we observed spontaneous regeneration of hair...

... full-length construct acts as a dominant-negative, downregulating both gdf7 and atoh1 . This is likely to be an indirect consequence of the demonstrable loss of cdelta1 in neural epithelium, consistent with evidence that high levels of Hes1 lead to a cell-autonomous reduction in delta...

... binding sites in the promoter. Notch inhibition also led to precocious differentiation of epithelial progenitors into secretory cell types, including large numbers of cells that expressed both Paneth and goblet cell markers. Analysis of Notch function in Atoh1 -deficient intestine demonstrated...

... horn bHLH Neuronal specification Mouse Atoh1 Neurog2 Ascl1 Formation of the neuronal network in the dorsal spinal cord requires the generation of correct numbers of neurons with specified identities. Regulation of this process starts early in nervous system development, as cells...