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Development. October 1, 2013; 140 (20): 4277-86.

Myb promotes centriole amplification and later steps of the multiciliogenesis program.

Tan FE , Vladar EK , Ma L , Fuentealba LC , Hoh R , Espinoza FH , Axelrod JD , Alvarez-Buylla A , Stearns T , Kintner C , Krasnow MA .

The transcriptional control of primary cilium formation and ciliary motility are beginning to be understood, but little is known about the transcriptional programs that control cilium number and other structural and functional specializations. One of the most intriguing ciliary specializations occurs in multiciliated cells (MCCs), which amplify their centrioles to nucleate hundreds of cilia per cell, instead of the usual monocilium. Here we report that the transcription factor MYB, which promotes S phase and drives cycling of a variety of progenitor cells, is expressed in postmitotic epithelial cells of the mouse airways and ependyma destined to become MCCs. MYB is expressed early in multiciliogenesis, as progenitors exit the cell cycle and amplify their centrioles, then switches off as MCCs mature. Conditional inactivation of Myb in the developing airways blocks or delays centriole amplification and expression of FOXJ1, a transcription factor that controls centriole docking and ciliary motility, and airways fail to become fully ciliated. We provide evidence that MYB acts in a conserved pathway downstream of Notch signaling and multicilin, a protein related to the S-phase regulator geminin, and upstream of FOXJ1. MYB can activate endogenous Foxj1 expression and stimulate a cotransfected Foxj1 reporter in heterologous cells, and it can drive the complete multiciliogenesis program in Xenopus embryonic epidermis. We conclude that MYB has an early, crucial and conserved role in multiciliogenesis, and propose that it promotes a novel S-like phase in which centriole amplification occurs uncoupled from DNA synthesis, and then drives later steps of multiciliogenesis through induction of Foxj1.

PubMed ID: 24048590
PMC ID: PMC3787764
Article link: Development.
Grant support: 5T32 GM07276 NIGMS NIH HHS , 5U01HL099995 NHLBI NIH HHS , R01 GM096021 NIGMS NIH HHSHoward Hughes Medical Institute , R01 GM098582 NIGMS NIH HHS , 5U01HL099995 NHLBI NIH HHS , U01 HL099995 NHLBI NIH HHS , R01 GM096021 NIGMS NIH HHS , R01 GM098582 NIGMS NIH HHS , T32 GM007276 NIGMS NIH HHS , 5T32 GM07276 NIGMS NIH HHSHoward Hughes Medical Institute

Genes referenced: cdh1 cdkn1a epha8 foxj1.2 gmnn lamtor2 mcc myb myc nkx2-1 notch1 npat odc1 pcnt shh sox2

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