ArticleThe Journal of clinical investigation2016
Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Compartment-specific regulation of stromal differentiation of the spleen in health and disease.Genes and immunity · 2026Review
- Splenic structural and functional abnormalities in individuals with NR5A1/SF-1 variants.Endocrine connections · 2025Article
- In-depth investigation of genome to refine QTL positions for spontaneous sex-reversal in XX rainbow trout.PloS one · 2025Article
- Splenic stromal niches in homeostasis and immunity.Nature reviews. Immunology · 2023Review
- Coevolution of the Tlx homeobox gene with medusa development (Cnidaria: Medusozoa).Communications biology · 2023Article
- Seahorse Male Pregnancy as a Model System to Study Pregnancy, Immune Adaptations, and Environmental Effects.International journal of molecular sciences · 2023Review
- Absence of Nkx2-3 induces ectopic lymphatic endothelial differentiation associated with impaired extramedullary stress hematopoiesis in the spleen.Frontiers in cell and developmental biology · 2023Article
- Retinoid metabolism: new insights.Journal of molecular endocrinology · 2022Review
- Expression characteristics and interaction networks of microRNAs in spleen tissues of grass carp (Ctenopharyngodon idella).PloS one · 2022Article
- Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis.Bioengineered · 2021Article
- Article
- Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes.Journal of developmental biology · 2020Review
- Cyp26b1 is an essential regulator of distal airway epithelial differentiation during lung development.Development (Cambridge, England) · 2020Article
- Long Non-Coding RNA BCAR4 Binds to miR-644a and Targets TLX1 to Promote the Progression of Bladder Cancer.OncoTargets and therapy · 2020Article
- RDH10-mediated retinol metabolism and RARα-mediated retinoic acid signaling are required for submandibular salivary gland initiation.Development (Cambridge, England) · 2018Article
- A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression.Nature communications · 2018Article
- Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia.Human molecular genetics · 2017Article
- Review
Corrections and comments
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Authors and funding
21 authors at 8 institutions in 6 countries.
Funding
Abstract
The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome P450 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insights into the molecular determinants of human congenital asplenia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.