Tfap2a Promotes Specification and Maturation of Neurons in the Inner Ear through Modulation of Bmp, Fgf and Notch Signaling

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Neurons of the statoacoustic ganglion (SAG) transmit impulses from the inner ear necessary for hearing and balance. SAG cells exhibit a complex pattern of development, regulation of which remains poorly understood. Here we show that transcription factor Tfap2a coordinates multiple cell signaling pathways needed to regulate the quantity and pace of SAG neuron production. SAG progenitors originate within the developing inner ear and then migrate out of the ear towards the hindbrain before forming mature neurons. We showed previously that Fgf initiates formation of SAG progenitors in the inner ear, but rising levels of Fgf signaling eventually terminate this process. Elevated Fgf also stimulates proliferation of SAG progenitors outside the ear and delays their maturation. Notch signaling is also known to limit SAG development. Tfap2a governs the strength of Fgf and Notch signaling by activating expression of Bmp7a, which inhibits Fgf and Notch. Together these signals stabilize the pool of SAG progenitors outside the ear by equalizing rates of maturation and proliferation. This balance is critical for sustained accumulation of SAG neurons during larval growth as well as regeneration following neural damage. These findings could inform development of stem cell therapies to correct auditory neuropathies in humans.

Vyšlo v časopise: Tfap2a Promotes Specification and Maturation of Neurons in the Inner Ear through Modulation of Bmp, Fgf and Notch Signaling. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005037
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005037

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