@article{274973ba40d445508e48919072bc203c,
title = "Tbx2 and Tbx3 regulate cell fate progression of the otic vesicle for inner ear development",
abstract = "The morphogenesis of the otic vesicle (OV) to form inner ear organs serves as an excellent model system to understand cell fate acquisition on a single cell level. Tbx2 and Tbx3 (Tbx2/3) encode closely related T-box transcription factors that are expressed widely in the mammalian OV. Inactivation of both genes in the OV (Tbx2/3cKO) results in failed morphogenesis into inner ear organs. To understand the basis of these defects, single cell RNA-sequencing (scRNA-seq) was performed on the OV lineage, in controls versus Tbx2/3cKO embryos. We identified a multipotent population termed otic progenitors in controls that are marked by expression of the known otic placode markers Eya1, Sox2, and Sox3 as well as new markers Fgf18, Cxcl12, and Pou3f3. The otic progenitor population was increased three-fold in Tbx2/3cKO embryos, concomitant with dysregulation of genes in these cells as well as reduced progression to more differentiated states of prosensory and nonsensory cells. An ectopic neural population of cells was detected in the posterior OV of Tbx2/3cKO embryos but had reduced maturation to delaminated neural cells. As all three cell fates were affected in Tbx2/3cKO embryos, we suggest that Tbx2/3 promotes progression of multipotent otic progenitors to more differentiated cell types in the OV.",
keywords = "Cell fate, Conditional knockout, Inner ear, Otic vesicle, Single-cell RNA-Sequencing, Tbx2, Tbx3",
author = "Hansoo Song and Morrow, {Bernice E.}",
note = "Funding Information: We thank Dr. Lu Zhang and Dr. Chenleng Cai for the generation of the Tbx2/3 floxed mice. We appreciate mentorship and helpful suggestions on this project from Dr. Pin-Xian Xu at Icahn School of Medicine at Mount Sinai, NY. We thank Dr. Christopher De Bono for scientific discussion and support in optimizing many of the experiments used in this study. We thank Dr. Deyou Zheng, Dr. Yang Liu, and Alexander Ferrena for scientific discussion and advice for bioinformatic analysis. We thank Dr. Andrew K. Groves for providing the Pax2-Cre mice. We thank the Genomics core, especially David Reynolds, Director of the Genomics Core, Shahina Maqbool, Director of the Flow Cytometry facilities at Einstein. We thank the Analytical Imaging Facility, especially Andrea Briceno and Hillary Guzik, funded by NCI Cancer Center Support Grant P30CA013330 . We would like to thank Dr. Charles Query, Director of the Training Program in Cellular and Molecular Biology and Genetics , 5T32GM007491 , for supporting the work of Hansoo Song. The work was also funded by the NIDCD, NIH Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31), F31DC019037 . Funding Information: We thank Dr. Lu Zhang and Dr. Chenleng Cai for the generation of the Tbx2/3 floxed mice. We appreciate mentorship and helpful suggestions on this project from Dr. Pin-Xian Xu at Icahn School of Medicine at Mount Sinai, NY. We thank Dr. Christopher De Bono for scientific discussion and support in optimizing many of the experiments used in this study. We thank Dr. Deyou Zheng, Dr. Yang Liu, and Alexander Ferrena for scientific discussion and advice for bioinformatic analysis. We thank Dr. Andrew K. Groves for providing the Pax2-Cre mice. We thank the Genomics core, especially David Reynolds, Director of the Genomics Core, Shahina Maqbool, Director of the Flow Cytometry facilities at Einstein. We thank the Analytical Imaging Facility, especially Andrea Briceno and Hillary Guzik, funded by NCI Cancer Center Support Grant P30CA013330. We would like to thank Dr. Charles Query, Director of the Training Program in Cellular and Molecular Biology and Genetics, 5T32GM007491, for supporting the work of Hansoo Song. The work was also funded by the NIDCD, NIH Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31), F31DC019037. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2023",
month = feb,
doi = "10.1016/j.ydbio.2022.12.003",
language = "English (US)",
volume = "494",
pages = "71--84",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
}