Abstract：
:Numerous signals drive the proliferative expansion of the distal endoderm and the underlying mesenchyme during lung branching morphogenesis, but little is known about how these signals are integrated. Here, we show by analysis of conditional double mutants that the two T-box transcription factor genes Tbx2 and Tbx3 act together in the lung mesenchyme to maintain branching morphogenesis. Expression of both genes depends on epithelially derived Shh signaling, with additional modulation by Bmp, Wnt, and Tgfβ signaling. Genetic rescue experiments reveal that Tbx2 and Tbx3 function downstream of Shh to maintain pro-proliferative mesenchymal Wnt signaling, in part by direct repression of the Wnt antagonists Frzb and Shisa3. In combination with our previous finding that Tbx2 and Tbx3 repress the cell-cycle inhibitors Cdkn1a and Cdkn1b, we conclude that Tbx2 and Tbx3 maintain proliferation of the lung mesenchyme by way of at least two molecular mechanisms: regulating cell-cycle regulation and integrating the activity of multiple signaling pathways.
journal_name
Dev Celljournal_title
Developmental cellauthors
Lüdtke TH,Rudat C,Wojahn I,Weiss AC,Kleppa MJ,Kurz J,Farin HF,Moon A,Christoffels VM,Kispert Adoi
10.1016/j.devcel.2016.08.007subject
Has Abstractpub_date
2016-10-24 00:00:00pages
239-253issue
2eissn
1534-5807issn
1878-1551pii
S1534-5807(16)30582-2journal_volume
39pub_type
杂志文章abstract：:In this issue of Developmental Cell, Chakraborty et al. report that efficient advancement through G1/S phase requires the downregulation of Nup96 levels during M phase. The authors show that oscillations in Nup96 levels plays a key role in maintaining normal cell proliferation, likely by regulating the export of speci...
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