Direct BMP2/4 signaling through BMP receptor IA regulates fetal thymocyte progenitor homeostasis and differentiation to CD4+CD8+ double-positive cell
Authors
Hager-Theodorides, Ariadne L.Ross, Susan
Sahni, Hemant
Mishina, Yuji
Furmanski, Anna L.
Crompton, Tessa
Issue Date
2013-11-18
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BMP2/4 signaling is required for embryogenesis and involved in thymus morphogenesis and T-lineage differentiation. In vitro experiments have shown that treatment of thymus explants with exogenous BMP4 negatively regulated differentiation of early thymocyte progenitors and the transition from CD4-CD8- (DN) to CD4+CD8+ (DP). Here we show that in vivo BMP2/4 signaling is required for fetal thymocyte progenitorhomeostasis and expansion, but negatively regulates differentiation from DN to DP cell. Unexpectedly, conditional deletion of BMPRIA from fetal thymocytes (using the Cre-loxP system and directing excision to hematopoietic lineage cells with the Vav promoter) demonstrated that physiological levels of BMP2/4 signaling directly to thymocytes through BMPRIA are required for normal differentiation and expansion of early fetal DN thymocytes. In contrast, the arrest in early thymocyte progenitor differentiation caused by exogenous BMP4 treatment of thymus explants is induced in part by direct signaling to thymocytes through BMPRIA, and in part by indirect signaling through non-hematopoietic cells. Analysis of the transition from fetal DN to DP cell, both by ex vivo analysis of conditional BMPRIA-deficient thymocytes and by treatment of thymus explants with the BMP4-inhibitor Noggin demonstrated that BMP2/4 signaling is a negative regulator at this stage. We showed that at this stage of fetal T-cell development BMP2/4 signals directly to thymocytes through BMPRIA.Citation
Hager-Theodorides AL, Ross SE, Sahni H, Mishina Y, Furmanski AL, Crompton T (2014) 'Direct BMP2/4 signaling through BMP receptor IA regulates fetal thymocyte progenitor homeostasis and differentiation to CD4+CD8+ double-positive cell', Cell Cycle, 13 (2), pp.324-333.Publisher
Taylor & FrancisJournal
Cell CycleDOI
10.4161/cc.27118PubMed ID
24240189PubMed Central ID
PMC3906248Additional Links
https://www.tandfonline.com/doi/abs/10.4161/cc.27118Type
ArticleLanguage
enISSN
1538-4101ae974a485f413a2113503eed53cd6c53
10.4161/cc.27118
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