Tbx2 and Tbx3 Act Downstream of Shh to Maintain Canonical Wnt Signaling during Branching Morphogenesis of the Murine Lung
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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.
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Upregulation of pioneer developmental organizers such as SOX2, KLF4, β-catenin, SNAIL-1, c-MYC, TBX3, and BCL6 is reported downstream of BRAF/MAPK-driven tumor.
“Even upregulation of pioneer developmental organizers, such as SOX2, KLF4, β-catenin, SNAIL-1, c-MYC, TBX3, BCL6, et al., are reported downstream of BRAF/MAPK-driven tumor, the pathways causing lineage reprogramming are not clear12,15,30–36.”
From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [33]
TBX3 and TBX2 are closely entangled in other regulatory programs, such as Wnt and Hedgehog signaling, and both are essential for proper limb, lung, and ureter development.
“TBX3 and TBX2 are closely entangled in other regulatory programs, such as Wnt and Hedgehog signaling, and both are essential for proper limb [8], lung [9], and ureter development [10].”
From TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration (2023) · cites this paper as [9]
Redundancy between Tbx3 and Tbx2 to compensate for each other has been reported in several organs.
“Interestingly, redundancy between Tbx3 and Tbx2 to compensate for each other has been reported in several organs [9, 10].”
From TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration (2023) · cites this paper as [9]
Tbx3 interacts with certain parts of the Wnt and Hedgehog signaling pathways.
“Interestingly, Tbx3 interacts with certain parts of the Wnt and Hedgehog signaling pathways [8–10].”
From TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration (2023) · cites this paper as [9]
Cites
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237 · see citing works
A global double-fluorescent Cre reporter mouse
Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L., & Luo, L. (2007) · genesis · doi:10.1002/dvg.20335 · Cited by 3,491 · see citing works
A molecular mechanism for the effect of lithium on development.
Klein, P. S., & Melton, D. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8455 · Cited by 2,305 · see citing works
Jho, E., Zhang, T., Domon–Dell, C., Joo, C., Freund, J., & Costantini, F. D. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1172-1183.2002 · Cited by 1,683 · see citing works
Small molecule–mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer
Chen, B., Dodge, M. E., Tang, W., Lü, J., Ma, Z., Fan, C.-W., Wei, S., Hao, W., Kilgore, J. A., Williams, N. S., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.137 · Cited by 1,385 · see citing works
Fibroblast Growth Factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung
Bellusci, S., Grindley, J. C., Emoto, H., Itoh, N., & Hogan, B. L. M. (1997) · Development · doi:10.1242/dev.124.23.4867 · Cited by 1,006 · see citing works
Preparing for the First Breath: Genetic and Cellular Mechanisms in Lung Development
Morrisey, E. E., & Hogan, B. L. M. (2010) · Developmental Cell · doi:10.1016/j.devcel.2009.12.010 · Cited by 967 · see citing works
Sonic hedgehog is essential to foregut development
Litingtung, Y., Li, L., Westphal, H., & Chiang, C. (1998) · Nature Genetics · doi:10.1038/1717 · Cited by 715 · see citing works
Sonic hedgehog regulates branching morphogenesis in the mammalian lung.
Pepicelli, C. V., Lewis, P. M., & McMahon, A. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70446-4 · Cited by 660 · see citing works
Long, F., Zhang, X. M., Karp, S. J., Yang, Y., & McMahon, A. P. (2001) · Development · doi:10.1242/dev.128.24.5099 · Cited by 654 · see citing works
The teratogenic Veratrum alkaloid cyclopamine inhibits Sonic hedgehog signal transduction
Incardona, J. P., Gaffield, W., Kapur, R. P., & Roelink, H. (1998) · Development · doi:10.1242/dev.125.18.3553 · Cited by 654 · see citing works
Secreted and transmembrane wnt inhibitors and activators
Cruciat, C.-M., & Niehrs, C. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a015081 · Cited by 646 · see citing works
Laping, N. J., Grygielko, E. T., Mathur, A., Butter, S., Bomberger, J. M., Tweed, C. W., Martin, W., Fornwald, J. A., Lehr, R. V., Harling, J. D., et al. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.1.58 · Cited by 638 · see citing works
Lung development: orchestrating the generation and regeneration of a complex organ
Herriges, M., & Morrisey, E. E. (2014) · Development · doi:10.1242/dev.098186 · Cited by 613 · see citing works
Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis
Bellusci, S., Furuta, Y., Rush, M., Henderson, R., Winnier, G. E., & Hogan, B. L. M. (1997) · Development · doi:10.1242/dev.124.1.53 · Cited by 579 · see citing works
Id Genes Are Direct Targets of Bone Morphogenetic Protein Induction in Embryonic Stem Cells
Hollnagel, A., Oehlmann, V. D., Heymer, J., Rüther, U., & Nordheim, A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.28.19838 · Cited by 523 · see citing works
Hébert, J. M., & McConnell, S. K. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9732 · Cited by 522 · see citing works
Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis
Weaver, M., Dunn, N. R., & Hogan, B. L. M. (2000) · Development · doi:10.1242/dev.127.12.2695 · Cited by 507 · see citing works
T-Box Genes in Vertebrate Development
Naiche, L. A., Harrelson, Z., Kelly, R. G., & Papaioannou, V. E. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.073003.105925 · Cited by 426 · see citing works
Correction to: The Brachyury gene encodes a novel DNA binding protein.
Kispert, A., & Hermann, B. G. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06179.x · Cited by 406 · see citing works
Self-citationHao, J., Ho, J. N., Lewis, J. A., Karim, K., Daniels, R. N., Gentry, P. R., Hopkins, C. R., Lindsley, C. W., & Hong, C. C. (2009) · ACS Chemical Biology · doi:10.1021/cb9002865 · Cited by 369 · see citing works
Wnt7b regulates mesenchymal proliferation and vascular development in the lung
Shu, W., Jiang, Y. Q., Lu, M. M., & Morrisey, E. E. (2002) · Development · doi:10.1242/dev.129.20.4831 · Cited by 354 · see citing works
Colvin, J. S., White, A. C., Pratt, S. J. P., & Ornitz, D. M. (2001) · Development · doi:10.1242/dev.128.11.2095 · Cited by 338 · see citing works
The Brachyury gene encodes a novel DNA binding protein.
Kispert, A., & Herrmann, B. G. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05990.x · Cited by 321 · see citing works
Self-citationSun, L., Tran, N., Liang, C., Tang, F. L. M., Rice, A. G., Schreck, R., Waltz, K., Shawver, L. K., McMahon, G., & Tang, C. (1999) · Journal of Medicinal Chemistry · doi:10.1021/jm9904295 · Cited by 261 · see citing works
White, A. C., Xu, J.-S., Yin, Y.-J., Smith, C. S., Schmid, G. J., & Ornitz, D. (2006) · Development · doi:10.1242/dev.02313 · Cited by 225 · see citing works
Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer
van den Boogaard, M., Wong, L. Y. E., Tessadori, F., Bakker, M. L., Dreizehnter, L., Wakker, V., Bezzina, C. R., Hoen, P. A. C. ’., Bakkers, J., Barnett, P., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62613 · Cited by 200 · see citing works
Self-citationWang, Z., Shu, W., Lu, M. M., & Morrisey, E. E. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.12.5022-5030.2005 · Cited by 193 · see citing works
Ågren, M., Kogerman, P., Kleman, M. I., Wessling, M., & Toftgård, R. (2004) · Gene · doi:10.1016/j.gene.2004.01.010 · Cited by 186 · see citing works
Yamamoto, A., Nagano, T., Takehara, S., Hibi, M., & Aizawa, S. (2005) · Cell · doi:10.1016/j.cell.2004.11.051 · Cited by 183 · see citing works
Cohen, E. D., Ihida‐Stansbury, K., Lu, M. M., Panettieri, R. A., Jones, P. L., & Morrisey, E. E. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38079 · Cited by 180 · see citing works
Aanhaanen, W. T. J., Brons, J. F., Dominguez, J. N., Rana, M. S., Norden, J., Airik, R., Wakker, V., Vries, C. D. G.-D., Brown, N. A., Kispert, A., et al. (2009) · Circulation Research · doi:10.1161/circresaha.108.192450 · Cited by 179 · see citing works
Self-citationSonic Hedgehog Signaling in the Lung. From Development to Disease
Kugler, M. C., Joyner, A. L., Loomis, C. A., & Munger, J. S. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2014-0132tr · Cited by 177 · see citing works
Current Therapies and Emerging Targets for the Treatment of Diabetes
Wagman, A., & Nuss, J. (2001) · Current Pharmaceutical Design · doi:10.2174/1381612013397915 · Cited by 175 · see citing works
Wnt5a regulates Shh and Fgf10 signaling during lung development
Li, C., Hu, L., Xiao, J., Chen, H., Li, J. T., Bellusci, S., Langhe, S. D., & Minoo, P. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.08.035 · Cited by 174 · see citing works
Rajagopal, J., Carroll, T. J., Guseh, J. S., Bores, S. A., Blank, L. J., Anderson, W. J., Yu, J., Zhou, Q., McMahon, A. P., & Melton, D. A. (2008) · Development · doi:10.1242/dev.015495 · Cited by 161 · see citing works
Eblaghie, M. C., Reedy, M. C., Oliver, T., Mishina, Y. M., & Hogan, B. L. M. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2005.12.006 · Cited by 150 · see citing works
Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation
Singh, R., Hoogaars, W. M. H., Barnett, P., Grieskamp, T., Rana, M. S., Buermans, H. P. J., Farin, H. F., Petry, M., Heallen, T. R., Martin, J. F., et al. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0884-2 · Cited by 145 · see citing works
Self-citationAn FGF-WNT gene regulatory network controls lung mesenchyme development.
Yin, Y.-J., White, A. C., Huh, S.-H., Hilton, M. J., Kanazawa, H., Long, F.-X., & Ornitz, D. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.04.009 · Cited by 140 · see citing works
Ribalta, T., McCutcheon, I. E., Aldape, K., Bruner, J. M., & Fuller, G. N. (2004) · The American Journal of Surgical Pathology · doi:10.1097/01.pas.0000141389.06925.d5 · Cited by 140 · see citing works
Sánchez‐Margalet, V., Goldfine, I. D., Vlahos, C. J., & Sung, C. K. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2480 · Cited by 134 · see citing works
FGF signaling regulates expression of Tbx2, Erm, Pea3, and Pax3 in the early nasal region.
Firnberg, N., & Neubüser, A. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0696 · Cited by 132 · see citing works
Wnt and FGF mediated epithelial‐mesenchymal crosstalk during lung development
Volckaert, T., & Langhe, S. D. (2014) · Developmental Dynamics · doi:10.1002/dvdy.24234 · Cited by 130 · see citing works
Yin, Y.-J., Wang, F., & Ornitz, D. (2011) · Development · doi:10.1242/dev.065110 · Cited by 120 · see citing works
Li, Y., Zhang, H., Choi, S. C., Litingtung, Y., & Chiang, C. C. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.03.009 · Cited by 107 · see citing works
Canonical Wnt signaling negatively regulates branching morphogenesis of the lung and lacrimal gland
Dean, C. H., Miller, L. D., Smith, A. N., Dufort, D., Lang, R. A., & Niswander, L. A. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.07.034 · Cited by 103 · see citing works
Goss, A., Tian, Y., Cheng, L., Yang, J., Zhou, D. D., Cohen, E. D., & Morrisey, E. E. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.06.011 · Cited by 91 · see citing works
TGF-β receptor II in epitheliaversusmesenchyme plays distinct roles in the developing lung
Chen, H., Zhuang, F., Liu, Y.-H., Xu, B., del Moral, P.-M., Deng, W., Chai, Y., Kolb, M. R. J., Gauldie, J., Warburton, D., et al. (2008) · European Respiratory Journal · doi:10.1183/09031936.00165407 · Cited by 85 · see citing works
Tbx2 Controls Lung Growth by Direct Repression of the Cell Cycle Inhibitor Genes Cdkn1a and Cdkn1b
Lüdtke, T. H., Farin, H. F., Rudat, C., Schuster-Gossler, K., Petry, M., Barnett, P., Christoffels, V. M., & Kispert, A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003189 · Cited by 79 · see citing works
Self-citationSignaling networks regulating development of the lower respiratory tract.Preprint
Ornitz, D., & Yin, Y.-J. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008318 · Cited by 77 · see citing works
Immunolocalization of Sonic Hedgehog (Shh) in Developing Mouse Lung
Miller, L. D., Wert, S. E., & Whitsett, J. A. (2001) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540104901213 · Cited by 74 · see citing works
Differential gene expression in the distal tip endoderm of the embryonic mouse lung
Liu, Y., & Hogan, B. L. M. (2002) · Gene Expression Patterns · doi:10.1016/s1567-133x(02)00057-1 · Cited by 71 · see citing works
Takabatake, Y., Takabatake, T., Sasagawa, S., & Takeshima, K. (2002) · Development Growth & Differentiation · doi:10.1046/j.1440-169x.2002.00640.x · Cited by 40 · see citing works
Mouse Tbx3 Mutants Suggest Novel Molecular Mechanisms for Ulnar-Mammary Syndrome
Frank, D. U., Emechebe, U., Thomas, K. R., & Moon, A. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067841 · Cited by 39 · see citing works
Self-citationLeconte, I., Fox, J. C., Baldwin, H. S., Buck, C. A., & Swain, J. L. (1998) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199812)213:4 · Cited by 38 · see citing works
Generation of mice with a conditional null allele for Tbx2
Wakker, V., Brons, J. F., Aanhaanen, W. T. J., van ROON, M. A., Moorman, A. F. M., & Christoffels, V. M. (2010) · genesis · doi:10.1002/dvg.20596 · Cited by 30 · see citing works
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Building and Regenerating the Lung Cell by Cell
Whitsett, J. A., Kalin, T. V., Xu, Y. J., & Kalinichenko, V. V. (2018) · Physiological Reviews · doi:10.1152/physrev.00001.2018 · Cited by 202 · see citing works
Karolak, J. A., Vincent, M., Deutsch, G. H., Gambin, T., Cogné, B., Pichon, O., Vetrini, F., Mefford, H. C., Dines, J. N., Golden‐Grant, K. L., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.12.010 · Cited by 165 · see citing works
Multifunctional neuron-specific enolase: its role in lung diseases
Xu, C., Luo, Y., Li, S., Li, Z., Jiang, L., Zhang, G., Owusu, L., & Chen, H. (2019) · Bioscience Reports · doi:10.1042/bsr20192732 · Cited by 114 · see citing works
The roles and regulation of TBX3 in development and disease
Khan, S. F., Damerell, V., Omar, R., Du Toit, M., Khan, M., Maranyane, H. M., Mlaza, M., Bleloch, J., Bellis, C., Sahm, B. D. B., et al. (2020) · Gene · doi:10.1016/j.gene.2019.144223 · Cited by 99 · see citing works
“Finally, Tbx2 and Tbx3 regulate mesenchymal proliferation by maintaining pro-proliferative Wnt signalling through direct repression of the Wnt antagonists Frzb and Shisa3 (Lüdtke et al., 2016).”
BackgroundCanonical Sonic Hedgehog Signaling in Early Lung Development
Fernandes-Silva, H., Correia‐Pinto, J., & Moura, R. S. (2017) · Journal of Developmental Biology · doi:10.3390/jdb5010003 · Cited by 89 · see citing works
Horie, M., Miyashita, N., Mikami, Y., Noguchi, S. F., Yamauchi, Y., Suzukawa, M., Fukami, T., Ohta, K., Asano, Y., Sato, S., et al. (2017) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00193.2017 · Cited by 55 · see citing works
Onishi, K., & Zou, Y. (2017) · eLife · doi:10.7554/elife.25269 · Cited by 49 · see citing works
Kaiser, M., Wojahn, I., Rudat, C., Lüdtke, T. H., Christoffels, V., Moon, A., Kispert, A., & Trowe, M.-O. (2021) · Development · doi:10.1242/dev.195651 · Cited by 42 · see citing works
Self-citationAydoğdu, N., Rudat, C., Trowe, M.-O., Kaiser, M., Lüdtke, T. H., Taketo, M. M., Christoffels, V. M., Moon, A., & Kispert, A. (2018) · Development · doi:10.1242/dev.171827 · Cited by 41 · see citing works
Self-citationEpithelial heparan sulfate regulates Sonic Hedgehog signaling in lung development
He, H., Huang, M., Sun, S., Wu, Y., & Lin, X. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006992 · Cited by 37 · see citing works
Karolak, J. A., Gambin, T., Honey, E. M., Slavík, T., Popek, E. J., & Stankiewicz, P. (2020) · BMC Medical Genomics · doi:10.1186/s12920-020-0701-6 · Cited by 33 · see citing works
Agley, C. C., Lewis, F., Jaka, O., Lazarus, N. R., Velloso, C. P., Francis‐West, P. H., Ellison, G. M., & Harridge, S. D. R. (2017) · Scientific Reports · doi:10.1038/s41598-017-10731-1 · Cited by 29 · see citing works
Li, P., Yang, C., Yin, J., Ge, M., Wang, S., Zhang, G., Zhang, Q., Xu, F., Dai, Z., Xie, L., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00636 · Cited by 28 · see citing works
Patterning the embryonic pulmonary mesenchyme
Goodwin, K., Jaslove, J. M., Tao, H., Zhu, M. S., Hopyan, S., & Nelson, C. M. (2022) · iScience · doi:10.1016/j.isci.2022.103838 · Cited by 27 · see citing works
Karolak, J. A., Gambin, T., Szafrański, P., & Stankiewicz, P. (2021) · Respiratory Research · doi:10.1186/s12931-021-01617-y · Cited by 25 · see citing works
Aminu, A. J., Petkova, M. A., Atkinson, A. J., Yanni, J., Morris, A. D., Simms, R. T., Chen, W., Yin, Z., Kuniewicz, M., Holda, M. K., et al. (2021) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2021.04.008 · Cited by 25 · see citing works
TBX2 controls a proproliferative gene expression program in melanomaPreprint
Lu, S., Louphrasitthiphol, P., Goradia, N., Lambert, J., Schmidt, J., Chauhan, J. S., Rughani, M. G., Larue, L., Wilmanns, M., & Goding, C. R. (2021) · Genes & Development · doi:10.1101/gad.348746.121 · Cited by 21 · see citing works
Li, Q., Jiao, J., Li, H., Wan, H., Zheng, C., Cai, J., & Bao, S. (2018) · Journal of Cell Science · doi:10.1242/jcs.217406 · Cited by 22 · see citing works
Epigenetic Suppression of the T-box Subfamily 2 (TBX2) in Human Non-Small Cell Lung Cancer
Nehme, E., Rahal, Z., Sinjab, A. F., Khalil, A., Chami, H. A., Nemer, G. M., & Kadara, H. N. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051159 · Cited by 22 · see citing works
The WNT7A/WNT7B/GPR124/RECK signaling module plays an essential role in mammalian limb development
Wang, Y., Venkatesh, A. K., Xu, J., Xu, M., Williams, J., Smallwood, P. M., James, A. W., & Nathans, J. (2022) · Development · doi:10.1242/dev.200340 · Cited by 20 · see citing works
TBX2subfamily suppression in lung cancer pathogenesis: a high-potential marker for early detection
Khalil, A., Sivakumar, S., Lucas, F. A. S., McDowell, T. L., Lang, W., Tabata, K., Fujimoto, J., Yatabe, Y., Spira, A. E., Scheet, P. A., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.19938 · Cited by 19 · see citing works
Exploring intrinsic variability between cultured nasal and bronchial epithelia in cystic fibrosis
Rodenburg, L. W., Metzemaekers, M., van der Windt, I. S., Smits, S. M. A., Oosterhoff, L. A., Kruisselbrink, E., Brunsveld, J. E., Heida-Michel, S., Groot, K. M. D. W., van der Ent, C. K., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-45201-4 · Cited by 16 · see citing works
Lüdtke, T. H., Wojahn, I., Kleppa, M., Schierstaedt, J., Christoffels, V. M., Künzler, P., & Kispert, A. (2021) · Respiratory Research · doi:10.1186/s12931-021-01679-y · Cited by 18 · see citing works
Self-citationIRF2BP2-deficient microglia block the anxiolytic effect of enhanced postnatal care
Hari, A., Cruz, S. A., Qin, Z., Couture, P., Vilmundarson, R. O., Huang, H., Stewart, A. F. R., & Chen, H. (2017) · Scientific Reports · doi:10.1038/s41598-017-10349-3 · Cited by 18 · see citing works
Broséus, L., Vaiman, D., Tost, J., Ruano, C. S. M., Jacobi, M., Schwartz, J. D., Béranger, R., Slama, R., Heude, B., & Lepeule, J. (2022) · BMC Medicine · doi:10.1186/s12916-022-02610-y · Cited by 16 · see citing works
TBX2-positive cells represent a multi-potent mesenchymal progenitor pool in the developing lung
Wojahn, I., Lüdtke, T. H., Christoffels, V. M., Trowe, M., & Kispert, A. (2019) · Respiratory Research · doi:10.1186/s12931-019-1264-y · Cited by 16 · see citing works
Self-citationZhang, Z., Wu, Y., Fu, J., Yu, X., Su, Y., Jia, S., Cheng, H., Shen, Y., He, X., Ren, K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48173-9 · Cited by 14 · see citing works
“ConsideringtheBRAF/MAPKinteraction with multiple developmental factors in tumorigenesis, such as β - catenin, Klf4, Sox2 et al. 10,33 – 35 , it would be interesting to investigate whether conserved regulations also apply.”
BackgroundTbx2 and Tbx3 regulate cell fate progression of the otic vesicle for inner ear development
Song, H., & Morrow, B. E. (2022) · Developmental Biology · doi:10.1016/j.ydbio.2022.12.003 · Cited by 14 · see citing works
ISL1 regulates lung branching morphogenesis via Shh signaling pathway
Huang, R., Zhang, C., Zheng, Y., Zhang, W., Huang, H., Qiu, M. S., Li, J., & Li, F. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105034 · Cited by 14 · see citing works
Khalil, A., Dekmak, B., Boulos, F. I., Kantrowitz, J., Spira, A. E., Fujimoto, J., Kadara, H. N., El-Hachem, N., & Nemer, G. M. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00482 · Cited by 14 · see citing works
The oncoprotein TBX3 is controlling severity in experimental arthritis
Sardar, S., Kerr, A., Vaartjes, D., Moltved, E. R., Karosiene, E., Gupta, R., & Andersson, Å. (2019) · Arthritis Research & Therapy · doi:10.1186/s13075-018-1797-3 · Cited by 13 · see citing works
“Renard CA, Labalette C, Armengol C, Cougot D, Wei Y, Cairo S, et al. Tbx3 is a downstream target of the Wnt/β-catenin pathway and a critical mediator of β-catenin survival functions in liver cancer.”
BackgroundHeterochronic regulation of lung development via the Lin28‐Let‐7 pathway
Gulman, N. K., Armon, L., Shalit, T., & Urbach, A. (2019) · The FASEB Journal · doi:10.1096/fj.201802702r · Cited by 13 · see citing works
Perrard, J., Morel, A., Meznad, K., Paget‐Bailly, P., Dalstein, V., Guenat, D., Mourareau, C., Clavel, C., Fauconnet, S., Baguet, A., et al. (2019) · Oncology Letters · doi:10.3892/ol.2019.11158 · Cited by 11 · see citing works
Nemer, G. M., & Khalil, A. (2019) · Drug Research · doi:10.1055/a-0873-3529 · Cited by 11 · see citing works
Li, M., Li, T., Jin, T., Chen, Y., Cheng, L., Liang, Q., Yan, S., Li, T., Ran, Q., & Chen, W. (2023) · Molecular Biology Reports · doi:10.1007/s11033-023-08870-y · Cited by 9 · see citing works
Single‐cell profiling of MC1R ‐inhibited melanocytes
Berns, H. M., Watkins‐Chow, D. E., Lu, S., Louphrasitthiphol, P., Zhang, T., Brown, K. M., Moura‐Alves, P., Goding, C. R., & Pavan, W. J. (2023) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.13141 · Cited by 9 · see citing works
Complex functional redundancy of Tbx2 and Tbx3 in mouse limb development
Lopatka, A., & Moon, A. (2022) · Developmental Dynamics · doi:10.1002/dvdy.484 · Cited by 6 · see citing works
Self-citationYu, T., Ning, J., Wang, F., Liu, G., Wang, Q., Xu, X. S., Wang, C., & Lu, X. (2023) · Marine Biotechnology · doi:10.1007/s10126-023-10247-y · Cited by 8 · see citing works
Establishment of the TBX-code reveals aberrantly activated T-box gene TBX3 in Hodgkin lymphoma
Nagel, S., & Meyer, C. (2021) · PLoS ONE · doi:10.1371/journal.pone.0259674 · Cited by 7 · see citing works
Spatiotemporal transcriptome atlas of developing mouse lung
Meng, X., Li, W., Xu, J., Yao, Y., Gong, A., Yang, Y., Qu, F., Guo, C., Zheng, H., Cui, G., et al. (2025) · 中国科学通报：英文版 · doi:10.1016/j.scib.2025.03.012 · Cited by 6 · see citing works
Arnott, M., Sampilo, N. F., & Song, J. L. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1356589 · Cited by 7 · see citing works
TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration
Melzer, M. K., Schirge, S., Gout, J., Arnold, F., Srinivasan, D., Burtscher, I., Allgöwer, C., Mulaw, M., Zengerling, F., Günes, C., et al. (2023) · BMC Biology · doi:10.1186/s12915-023-01553-x · Cited by 5 · see citing works
“Indeed, important roles for TBX3 have been shown in lung branching morphogenesis and ureter organogenesis [9, 10].”
BackgroundMethodResultInfluentialSelf-citationJia, X., Huang, J., Wu, B., Yang, M., & Xu, W. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.745715 · Cited by 5 · see citing works
Singh, S., Budiman, T., Redmond, D., & Gupta, V. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000368 · Cited by 5 · see citing works
Atypical mesenchyme in congenital pulmonary airways malformation: a promising new focus
Azar, P., Avila, Y., Hiltbrunner, A., Delacourt, C., Rougemont, A., Vidal, I., Bochaton‐Piallat, M., & Ruchonnet-Métrailler, I. (2025) · Respiratory Research · doi:10.1186/s12931-025-03332-4 · Cited by 4 · see citing works
The molecular and cellular choreography of early mammalian lung development
Yang, X., Chen, Y., Yang, Y., Li, S., Mi, P., & Jing, N. (2024) · Medical Review · doi:10.1515/mr-2023-0064 · Cited by 3 · see citing works
Zeng, H., Ali, S., Sebastian, A., Ramos-Medero, A. S., Albert, I. U., Dean, C. H., & Liu, A. (2024) · Developmental Biology · doi:10.1016/j.ydbio.2024.07.006 · Cited by 3 · see citing works
Molecular Bases for Lung Development, Injury, and Repair
WU, S. M., & Savani, R. C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-54605-8.00001-5 · Cited by 3 · see citing works
Zhou, J., Lou, X., Wei, Z., Mao, X., Zhang, J., Jin, X., Li, B., Zheng, C., Siwu, X., Yang, Y., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02501-8 · Cited by 2 · see citing works
Tbx genes influence early gene expression and photoreceptor patterning in the chick retina
Ayten, M., Joisher, H. N. V., Prabhakara, C., & Cepko, C. L. (2026) · Developmental Biology · doi:10.1016/j.ydbio.2026.02.005 · Cited by 2 · see citing works
Loss of Tbx3 in Mouse Eye Causes Retinal Angiogenesis Defects Reminiscent of Human Disease
Derbyshire, M., Akula, S., Wong, A., Rawlins, K., Voura, E., Brunken, W., Zuber, M., Fuhrmann, S., Moon, A., & Viczian, A. (2023) · Investigative Ophthalmology and Visual Science · doi:10.1167/iovs.64.5.1 · Cited by 1 · see citing works
Self-citationExpression and prognosis analysis of TBX2 subfamily in human lung carcinoma
Mi, R., Wang, Q., Liu, Q., Jiang, F., & Ji, Y. (2024) · Discover Oncology · doi:10.1007/s12672-024-00900-w · Cited by 2 · see citing works
Wnt deregulation in rhabdomyosarcoma
Adhikari, A., & Davie, J. K. (2019) · Stem Cell Investigation · doi:10.21037/sci.2019.06.03 · Cited by 2 · see citing works
A Fetus with 17q23.1-q23.2 Microdeletion Presents with Primary Bilateral Lung Hypoplasia in Utero
Yao, L., Xu, Y., Deng, Y., & Zeng, S. (2022) · Fetal and Pediatric Pathology · doi:10.1080/15513815.2022.2069893 · Cited by 1 · see citing works
HOXA5-driven transcriptional program in lung development
Frenette, B., Guéno, J., Houde, N., Mansfield, J. H., & Jeannotte, L. (2025) · Developmental Biology · doi:10.1016/j.ydbio.2025.08.010 · Cited by 1 · see citing works
Genetic Anomalies of the Respiratory Tract
Cuppari, C., Cutrupi, M. C., Salpietro, A., Sallemi, A., Fusco, M., Parisi, G. F., & Salpietro, C. D. (2019) · Current Respiratory Medicine Reviews · doi:10.2174/1573398x15666191022100525
Studying the Effect of Low Doses of Ionization Radiation on Senescence in Human Lung Fibroblasts.
Kabilan, U. (2020) · uO Research (University of Ottawa) · doi:10.20381/ruor-25207
Loss of MC1R signaling implicates TBX3 in pheomelanogenesis and melanoma predispositionPreprint
Berns, H. M., Watkins‐Chow, D. E., Lu, S., Louphrasitthiphol, P., Zhang, T., Brown, K. M., Moura‐Alves, P., Goding, C. R., & Pavan, W. J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.10.532018
Transcriptomic analyses reveal regional signatures in lung allograft recipientsPreprint
Agudelo‐Romero, P., Ling, K., Lavender, M. A., Wrobel, J. P., Musk, M., Stick, S. M., & Kicic, A. (2023) · medRxiv · doi:10.1101/2023.04.03.23288063
Broséus, L., Vaiman, D., Tost, J., Ruano, C. S. M., Jacobi, M., Schwartz, J. D., Béranger, R., Slama, R., Heude, B., & Lepeule, J. (2022) · Figshare · doi:10.6084/m9.figshare.21376327
Li, T., Li, M., Feng, J., Liu, T., Yang, L., & Yu, L. (2024) · BMC Pediatrics · doi:10.1186/s12887-024-04852-6
Exploiting mechanisms for hierarchical branching structure of lung airway
Takigawa-Imamura, H., Fumoto, K., Takesue, H., & Miura, T. (2024) · PLoS ONE · doi:10.1371/journal.pone.0309464
Khalil, A., Dinh, T., Parks, M., Obeng, R. C., Gryder, B. E., Kresak, A. M., Wang, Y., Maltas, J., Bedrock, M., Wei, X., et al. (2025) · Genes & Diseases · doi:10.1016/j.gendis.2025.101840
Melzer, M. K., Schirge, S., Gout, J., Arnold, F., Srinivasan, D., Burtscher, I., Allgöwer, C., Mulaw, M., Zengerling, F., Güneş, Ç., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26576153
Self-citationKarolak, J. A., Gambin, T., Szafrański, P., & Stankiewicz, P. (2021) · Figshare · doi:10.6084/m9.figshare.13627451
Lüdtke, T. H., Wojahn, I., Kleppa, M.-J., Schierstaedt, J., Christoffels, V. M., Künzler, P., & Kispert, A. (2021) · Figshare · doi:10.6084/m9.figshare.14235003
Self-citationMelzer, M. K., Schirge, S., Gout, J., Arnold, F., Srinivasan, D., Burtscher, I., Allgöwer, C., Mulaw, M., Zengerling, F., Güneş, Ç., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26576156
Self-citationMelzer, M. K., Schirge, S., Gout, J., Arnold, F., Srinivasan, D., Burtscher, I., Allgöwer, C., Mulaw, M., Zengerling, F., Güneş, Ç., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26576162
Self-citationMelzer, M. K., Schirge, S., Gout, J., Arnold, F., Srinivasan, D., Burtscher, I., Allgöwer, C., Mulaw, M., Zengerling, F., Güneş, Ç., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26576159
Self-citationBroséus, L., Vaiman, D., Tost, J., Ruano, C. S. M., Jacobi, M., Schwartz, J. D., Béranger, R., Slama, R., Heude, B., & Lepeule, J. (2022) · Figshare · doi:10.6084/m9.figshare.21376324
Ontogeny of the enteric nervous system
Boismoreau, F. (2020) · doi:10.70675/b24ef52fz17c8z48e3za3afz5cc386550b86
- Authors
- Lüdtke, T. H., Rudat, C., Wojahn, I., Weiss, A.-C., Kleppa, M.-J., Kurz, J., Farin, H. F., Moon, A., Christoffels, V. M., & Kispert, A.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- University of Utah (US)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Kispert, Andreas
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 39
- Issue
- 2
- Pages
- 239-253
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2530410463
- Cited by
- 69
- References
- 56
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 7 · 2021: 10 · 2020: 3 · 2019: 13 · 2018: 4 · 2017: 7
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (DFG KI728/11)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- TBX2, TBX3, lung branching morphogenesis, Wnt/β-catenin signaling, Sonic hedgehog signaling, lung mesenchyme, BMP signaling, TGF-beta signaling, FRZB, p21, p27, cell cycle regulation, mesenchymal cell proliferation, signaling pathway integration
- MeSH terms
- Frizzled-Related Proteins, Animals, Female, Glycoproteins, Humans, Lung, Male, Mesoderm, Morphogenesis, Repressor Proteins, Transforming Growth Factor beta, Bone Morphogenetic Proteins, T-Box Domain Proteins, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Mice, Hedgehog Proteins, Wnt Signaling Pathway
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