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Tbx2 is a master regulator of inner versus outer hair cell di
AAV-Tbx2s was used for gene over-expression. (From BrainVTA)
The viruses used in this article from BrainVTA are in the table below
Custom-Made AAV  rAAV-CMV-Tbx2-IRES-mCherry-WPREs (AAV Anc80)
Jaime García-Añoveros, John C Clancy, Chuan Zhi Foo, Ignacio García-Gómez, Yingjie Zhou, Kazuaki Homma, Mary Ann Cheatham, Anne Duggan
Pub Date: 2022-05-04, DOI: 10.1038/s41586-022-04668-3, Email: [email protected]
The cochlea uses two types of mechanosensory cell to detect sounds. A single row of inner hair cells (IHCs) synapse onto neurons to transmit sensory information to the brain, and three rows of outer hair cells (OHCs) selectively amplify auditory inputs1. So far, two transcription factors have been implicated in the specific differentiation of OHCs, whereas, to our knowledge, none has been identified in the differentiation of IHCs2,3,4. One such transcription factor for OHCs, INSM1, acts during a crucial embryonic period to consolidate the OHC fate, preventing OHCs from transdifferentiating into IHCs2. In the absence of INSM1, embryonic OHCs misexpress a core set of IHC-specific genes, which we predict are involved in IHC differentiation. Here we find that one of these genes, Tbx2, is a master regulator of IHC versus OHC differentiation in mice. Ablation of Tbx2 in embryonic IHCs results in their development as OHCs, expressing early OHC markers such as Insm1 and eventually becoming completely mature OHCs in the position of IHCs. Furthermore, Tbx2 is epistatic to Insm1: in the absence of both genes, cochleae generate only OHCs, which suggests that TBX2 is necessary for the abnormal transdifferentiation of INSM1-deficient OHCs into IHCs, as well as for normal IHC differentiation. Ablation of Tbx2 in postnatal, largely differentiated IHCs makes them transdifferentiate directly into OHCs, replacing IHC features with those of mature and not embryonic OHCs. Finally, ectopic expression of Tbx2 in OHCs results in their transdifferentiation into IHCs. Hence, Tbx2 is both necessary and sufficient to make IHCs distinct from OHCs and maintain this difference throughout development.
Figure 1. Tbx2 is epistatic to Insm1.
In this study, the authors reported that Tbx2 is a master regulator of inner hair cells(IHC) versus outer hair cells(OHC) differentiation in mice.

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