The Mn1 transcription factor acts upstream of Tbx22 and preferentially regulates posterior palate growth in mice
Author:
Liu Wenjin1, Lan Yu1, Pauws Erwin2, Meester-Smoor Magda A.3, Stanier Philip2, Zwarthoff Ellen C.3, Jiang Rulang1
Affiliation:
1. Department of Biomedical Genetics and Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. 2. Institute of Child Health, University College London, London WC1N 1EH,UK. 3. Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam,The Netherlands.
Abstract
The mammalian secondary palate exhibits morphological, pathological and molecular heterogeneity along the anteroposterior axis. Although the cell proliferation rates are similar in the anterior and posterior regions during palatal outgrowth, previous studies have identified several signaling pathways and transcription factors that specifically regulate the growth of the anterior palate. By contrast, no factor has been shown to preferentially regulate posterior palatal growth. Here, we show that mice lacking the transcription factor Mn1 have defects in posterior but not anterior palatal growth. We show that Mn1 mRNA exhibits differential expression along the anteroposterior axis of the developing secondary palate, with preferential expression in the middle and posterior regions during palatal outgrowth. Extensive analyses of palatal gene expression in wild-type and Mn1-/- mutant mice identified Tbx22, the mouse homolog of the human X-linked cleft palate gene, as a putative downstream target of Mn1 transcriptional activation. Tbx22 exhibits a similar pattern of expression with that of Mn1 along the anteroposterior axis of the developing palatal shelves and its expression is specifically downregulated in Mn1-/- mutants. Moreover, we show that Mn1 activated reporter gene expression driven by either the human or mouse Tbx22gene promoters in co-transfected NIH3T3 cells. Overexpression of Mn1in NIH3T3 cells also increased endogenous Tbx22 mRNA expression in a dose-dependent manner. These data indicate that Mn1 and Tbx22 function in a novel molecular pathway regulating mammalian palate development.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference59 articles.
1. Alappat, S. R., Zhang, Z., Suzuki, K., Zhang, X., Liu, H.,Jiang, R., Yamada, G. and Chen, Y. (2005). The cellular and molecular etiology of the cleft secondary palate in Fgf10 mutant mice. Dev. Biol.277,102-113. 2. Andreou, A. M., Pauws, E., Jones, M. C., Singh, M. K., Bussen,M., Doudney, K., Moore, G. E., Kispert, A., Brosens, J. J. and Stanier, P.(2007). TBX22 missense mutations found in patients with X-linked cleft palate affect DNA binding, sumoylation, and transcriptional repression. Am. J. Hum. Genet.81,700-712. 3. Braybrook, C., Doudney, K., Marçano, A. C., Arnason, A.,Bjornsson, A., Patton, M. A., Goodfellow, P. J., Moore, G. E. and Stanier,P. (2001). The T-box transcription factor gene TBX22is mutated in X-linked cleft palate and ankyloglossia. Nat. Genet.29,179-183. 4. Braybrook, C., Lisgo, S., Doudney, K., Henderson, D.,Marçano, A. C., Strachan, T., Patton, M. A., Villard, L., Moore, G. E.,Stanier, P. et al. (2002). Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia phenotype observed in CPX patients. Hum. Mol. Genet.11,2793-2804. 5. Buijs, A., Sherr, S., van Baal, S., van Bezouw, S., van der Plas, D., Geurts van Kessel, A., Riegman, P., Lekanne Deprez, R., Zwarthoff,E. and Hagemeijer, A. (1995). Translocation (12;22) (p13;q11)in myeloproliferative disorders results in fusion of the ETS-like TELgene on 12p13 to the MN1 gene on 22q11. Oncogene10,1511-1519.
Cited by
63 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|