...; 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 The inner ear sensory organs, which...

...., 2009 ; Rose et al., 2009 ), the rhombic lip of the cerebellar anlage (rhombomere 1) is the exclusive source of granule cell precursors that then migrate tangentially to form the EGL ( Wingate and Hatten, 1999 ). The cells in the rhombic lip that contribute to the EGL already express Atoh1 , which...

...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...

... for release after 6 months. We thank Domingos Henrique and David Ish-Horowitz for expression constructs, and Alessio Delogu for his help with cloning strategies. The dynamic maintenance of the roof plate organiser corresponds with our observations that an atoh1 -positive rhombic lip is acutely...

... 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...

... Mouse Atoh1 Neurog2 Ascl1 The circuitry of the nervous system depends on complex connections of diverse neuronal cell types. Thus, defining the mechanisms that regulate neuronal diversity is fundamental for understanding how the nervous system functions. Specification of distinct neuronal sub...