# A Tale from TGF-β Superfamily for Thymus Ontogeny and Function **Authors:** Arnon Dias Jurberg, Larissa Vasconcelos-Fontes, Vinícius Cotta-de-Almeida PMC · DOI: 10.3389/fimmu.2015.00442 · Frontiers in Immunology · 2015-09-10 ## TL;DR This review explores how TGF-β and related proteins influence thymus development and function, including their role in reversing aging effects. ## Contribution The paper provides a novel ontogenetic perspective on TGF-β superfamily signaling in thymus development and aging. ## Key findings - TGF-β and BMP ligands are critical for thymus morphogenesis and T cell differentiation. - GDF11 shows potential in reversing aging-related thymic decline. - The review highlights the importance of signaling pathways in thymus function across life. ## Abstract Multiple signaling pathways control every aspect of cell behavior, organ formation, and tissue homeostasis throughout the lifespan of any individual. This review takes an ontogenetic view focused on the large superfamily of TGF-β/bone morphogenetic protein ligands to address thymus morphogenesis and function in T cell differentiation. Recent findings on a role of GDF11 for reversing aging-related phenotypes are also discussed. ## Linked entities - **Proteins:** TGFB1 (transforming growth factor beta 1), GDF11 (growth differentiation factor 11) ## Full-text entities - **Genes:** Cdc42 (cell division cycle 42) [NCBI Gene 12540], Stat5a (signal transducer and activator of transcription 5A) [NCBI Gene 20850] {aka STAT5}, Vav1 (vav guanine nucleotide exchange factor 1) [NCBI Gene 22324] {aka Vav, vav-T}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, Bcl2l11 (BCL2 like 11) [NCBI Gene 12125] {aka 1500006F24Rik, Bim, Bod, bcl2-L-11}, Tgfbr3 (transforming growth factor, beta receptor III) [NCBI Gene 21814] {aka 1110036H20Rik, TBRIII}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, Cripto (cripto, EGF-CFC family member) [NCBI Gene 21667] {aka CR1, Tdgf1}, Acvr1c (activin A receptor, type IC) [NCBI Gene 269275] {aka ACTR-IC, ACVRLK7, ALK7, Alk-7, C230097P10}, Bmpr2 (bone morphogenetic protein receptor type 2) [NCBI Gene 12168] {aka 2610024H22Rik, BMP-2, BMPR-2, BMPR-II, BMPRII, BRK-3}, Foxn1 (forkhead box N1) [NCBI Gene 15218] {aka D11Bhm185e, Fkh19, HFH-11, Hfh11, Whn, nu}, Acvr2a (activin A receptor type 2A) [NCBI Gene 29263] {aka Acvr2, rActR-II}, Epcam (epithelial cell adhesion molecule) [NCBI Gene 17075] {aka CD326, EGP, EGP-2, Egp314, Ep-CAM, EpCAM1}, Cd3e (CD3 antigen, epsilon polypeptide) [NCBI Gene 12501] {aka CD3, CD3epsilon, T3e}, Smad9 (SMAD family member 9) [NCBI Gene 55994] {aka MADH6, Madh8, Madh9, Smad8}, Bmp6 (bone morphogenetic protein 6) [NCBI Gene 12161] {aka D13Wsu115e, Vgr1}, Foxg1 (forkhead box G1) [NCBI Gene 15228] {aka 2900064B05Rik, BF-1, Bf1, Hfh9, Hfhbf1}, H2 (histocompatibility-2, MHC) [NCBI Gene 111364] {aka H-2, MHC-II}, Foxn1 (forkhead box N1) [NCBI Gene 287469] {aka RONU, Rnu, Whn}, Gdf15 (growth differentiation factor 15) [NCBI Gene 23886] {aka MIC-1, NAG-1, SBF}, Amh (anti-Mullerian hormone) [NCBI Gene 11705] {aka MIS}, Cd27 (CD27 antigen) [NCBI Gene 21940] {aka S152, Tnfrsf7, Tp55}, Smad6 (SMAD family member 6) [NCBI Gene 17130] {aka Madh6, b2b390Clo}, Tgfbr1 (transforming growth factor, beta receptor 1) [NCBI Gene 29591] {aka Alk5, Skr4, Tgfr-1, tbetaR-I}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, Smad2 (SMAD family member 2) [NCBI Gene 17126] {aka 7120426M23Rik, Madh2, Madr2, Smad-2, mMad2}, Gdf11 (growth differentiation factor 11) [NCBI Gene 14561] {aka BMP-11, Bmp11}, Ccl25 (C-C motif chemokine ligand 25) [NCBI Gene 20300] {aka A130072A22Rik, CKb15, Scya25, TECK}, Cd4 (Cd4 molecule) [NCBI Gene 24932] {aka W3/25, p55}, FOXN1 (forkhead box N1) [NCBI Gene 8456] {aka FKHL20, RONU, TIDAND, TIDTA, TLIND, WHN}, Tgfb3 (transforming growth factor, beta 3) [NCBI Gene 21809] {aka TGF-beta-3, Tgfb-3}, Foxa2 (forkhead box A2) [NCBI Gene 15376] {aka HNF3-beta, HNF3beta, Hnf-3b, Hnf3b, Tcf-3b, Tcf3b}, Lefty2 (left-right determination factor 2) [NCBI Gene 320202] {aka 6030463A22Rik, Ebaf, Lefta, Leftb, lefty-2, lefty-B}, Fgf7 (fibroblast growth factor 7) [NCBI Gene 29348] {aka Fgf5b, KGF/FGF7, Kgf}, GDF11 (growth differentiation factor 11) [NCBI Gene 10220] {aka BMP-11, BMP11, VHO}, Inha (inhibin alpha) [NCBI Gene 16322], Cd1d1 (CD1d1 antigen) [NCBI Gene 12479] {aka CD1.1, Cd1a, Cd1d, Ly-38}, FOXG1 (forkhead box G1) [NCBI Gene 396110] {aka CBF-1, FKHL1, FOXG1B, Qin}, Ccr9 (C-C motif chemokine receptor 9) [NCBI Gene 12769] {aka A130091K22Rik, Cmkbr10, GPR-9-6}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, Cd80 (CD80 antigen) [NCBI Gene 12519] {aka B71, Cd28l, Ly-53, Ly53, MIC17, TSA1}, Gdf6 (growth differentiation factor 6) [NCBI Gene 242316] {aka BMP-13, BMP13, GDF16}, Sox2 (SRY (sex determining region Y)-box 2) [NCBI Gene 20674] {aka Sox-2, lcc, ysb}, Tgfb2 (transforming growth factor, beta 2) [NCBI Gene 21808] {aka Tgf-beta2, Tgfb-2}, Psmb11 (proteasome (prosome, macropain) subunit, beta type, 11) [NCBI Gene 73902] {aka 5830406J20Rik, beta5t}, Cdx2 (caudal type homeobox 2) [NCBI Gene 12591] {aka Cdx-2}, Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Enpep (glutamyl aminopeptidase) [NCBI Gene 13809] {aka 6030431M22Rik, APA, Bp-1/6C3, Ly-51, Ly51}, Gcm2 (glial cells missing homolog 2) [NCBI Gene 107889] {aka Gcm-rs1, Gcm1, Gcm1-rs2}, Tgfbr1 (transforming growth factor, beta receptor I) [NCBI Gene 21812] {aka ALK5, Alk-5, ESK2, TGFR-1, TbetaR-I, TbetaRI}, Wnt4 (wingless-type MMTV integration site family, member 4) [NCBI Gene 22417] {aka Wnt-4}, BMP4 (bone morphogenetic protein 4) [NCBI Gene 396165] {aka BMP-4}, Gdf7 (growth differentiation factor 7) [NCBI Gene 238057] {aka BMP12}, Tcra (T cell receptor alpha chain) [NCBI Gene 21473] {aka Tcralpha}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, Cpap (centrosome assembly and centriole elongation protein) [NCBI Gene 219103] {aka 4932437H03Rik, Cenpj, Gm81, LAP, LIP1, Sas4}, Bmp5 (bone morphogenetic protein 5) [NCBI Gene 12160] {aka se}, Dll4 (delta like canonical Notch ligand 4) [NCBI Gene 54485] {aka Delta4}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4} - **Diseases:** infection (MESH:D007239), atrophy (MESH:D001284), FTOC (MESH:C564768), cleft palate (MESH:D002972), cardiac hypertrophy (MESH:D006332), hydrocephalus (MESH:D006849), embryonic lethality (MESH:D020964), thymic hypoplasia (MESH:D013953), agenesis (MESH:C536482), inflammation (MESH:D007249), hypoplasia (MESH:D000080344), tumorigenesis (MESH:D063646), SCID (MESH:D016511), TEC (MESH:C536905), renal defects (MESH:C537754) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Gallus gallus (bantam, species) [taxon 9031], Homo sapiens (human, species) [taxon 9606], Aggregatibacter actinomycetemcomitans (species) [taxon 714], Rattus norvegicus (brown rat, species) [taxon 10116] - **Cell lines:** BK5 — Gallus gallus (Chicken), Chicken bursal lymphoma, Cancer cell line (CVCL_T475), DN3 — Homo sapiens (Human), Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, Induced pluripotent stem cell (CVCL_9S55), FTOC — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_JZ57), E14.0 — Homo sapiens (Human), Familial hypertrophic cardiomyopathy type 26, Induced pluripotent stem cell (CVCL_A6XE) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC4564722/full.md ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4564722/full.md ## References 221 references — full list in the complete paper: https://tomesphere.com/paper/PMC4564722/full.md --- Source: https://tomesphere.com/paper/PMC4564722