Ask about this productRelated genes to: GLI1 antibody
- Gene:
- GLI1 NIH gene
- Name:
- GLI family zinc finger 1
- Previous symbol:
- GLI
- Synonyms:
- -
- Chromosome:
- 12q13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2016-01-15
Related products to: GLI1 antibody
Related articles to: GLI1 antibody
- The periodontal ligament (PDL) contains heterogeneous mesenchymal stem/progenitor cells that contribute to periodontal homeostasis and regeneration. However, the developmental origin and behavior of α-smooth muscle actin (αSMA)-positive cells remain poorly understood. This study investigated the spatiotemporal distribution of αSMA-positive cells during tooth development and their response to altered mechanical loading following extraction of the opposing mandibular molars in mice. Before tooth eruption, αSMA-positive cells were widely distributed throughout the dental follicles but became progressively restricted to the apical PDL during root formation and eruption. In contrast, c-kit immunoreactivity gradually disappeared from the apical PDL, whereas Gli1/tdTomato-positive cells partially co-localized with αSMA-positive cells. Following extraction of the opposing molars, the αSMA-positive area and the number of PCNA-positive cells transiently increased, while endomucin-positive blood vessels became dilated in the apical PDL. These findings demonstrate that αSMA-positive cells undergo dynamic developmental redistribution and rapidly respond to altered mechanical loading. Furthermore, the partial co-localization of αSMA and Gli1 suggests that at least a subset of αSMA-positive cells may represent a resident mechanosensitive mesenchymal progenitor population involved in periodontal homeostasis and remodeling, providing new insight into the biological basis of periodontal remodeling during orthodontic tooth movement and periodontal regeneration. - Source: PubMed
Publication date: 2026/08/21
Maruoka HaruhiHasegawa TomokaHongo HiromiYamamoto TomomayaAbe MikiKitakamae-Haraguchi MaiIrie KazuharuMizoguchi ToshihideLi MinqiHosoya AkihiroSato YoshiakiAmizuka Norio - The two principal collagen receptors in bone, the collagen-binding β1 integrins and discoidin domain receptor 2 (DDR2), each have important roles in development, but their functions in bone regeneration are largely unexplored. Using a critical-size calvarial defect model, we assessed the relative roles of these two receptor classes in BMP2-induced regeneration using a conditional knockout approach where Itgb1 (encodes integrin β1) and/or Ddr2 were selectively inactivated in GLI1 skeletal progenitor cells (SPCs). Inactivating either Itgb1 or Ddr2 partially inhibited calvarial regeneration, while inactivation of both receptors almost completely blocked bone healing. Responses were linked to reduced proliferation and migration of GLI1 SPCs into defects and reduced endochondral and intramembranous bone formation. To examine the consequences of receptor inactivation at the cellular level, calvarial SPCs lacking Itgb1, Ddr2 or both receptors were generated. Loss of either receptor inhibited osteoblast differentiation, migration, cell spreading, focal adhesion formation, and nuclear localization of the mechanotransducer, YAP1. Importantly, inactivation of both receptors inhibited responses to a greater extent than was seen with individual knockouts. Interestingly, while inactivation of one allele of either Itgb1 (Itgb1) or Ddr2 (Ddr2) did not affect any of the above parameters, inactivation in double heterozygotes (Itgb1 ;Ddr2) was strongly inhibitory, which is indicative of a genetic interaction between Itgb1 and Ddr2. Lastly, immunofluorescence and immunoprecipitation analysis suggest that DDR2 and ITGB1 physically interact, providing a potential explanation for the observed functional cooperativity. These studies provide a mechanistic basis for bone regeneration strategies involving combined activation of integrin β1 and DDR2. - Source: PubMed
Publication date: 2026/08/18
Han YuanyuanGe ChunxiKamath Rajay AKaartinen VesaFranceschi Renny T - Congenital anomalies often arise during critical developmental time windows, yet the underlying mechanisms remain unclear. Here, we identify a time-specific FGFR2-retinoic acid signaling axis regulating postnatal coronal suture development through dura mater-suture mesenchyme interactions. FGFR2 signaling gradually declines after birth, leading to reduced retinoic acid signaling by moderating the expression of Aldh1a3 in the dura mater and suture mesenchyme alongside that of Rbp1 in the dura mater, thereby preserving GLI1+ progenitors and restraining osteogenesis to maintain suture patency. Importantly, FGFR2 overactivation in Fgfr2IIIc mutant mice within an early time window, disrupts this physiological FGFR2-retinoic acid signaling decline by upregulating Rbp1 and Aldh1a3 through enhanced P38 signaling. This leads to increased retinoic acid synthesis, premature osteogenic differentiation of GLI1+ progenitors, and coronal suture craniosynostosis. Significantly, genetic restoration of retinoic acid signaling rescues craniosynostosis in Fgfr2IIIc mutant mice, confirming retinoic acid signaling as a key downstream effector of FGFR2 signaling. Notably, restoration of suture patency alone rescues neurocognitive dysfunctions in Fgfr2IIIc mutant mice despite Fgfr2 mutation in the brain, demonstrating that the neurocognitive impairments primarily arise from cranial structural constraints and elevated intracranial pressure rather than intrinsic neural defects. This critical postnatal time window in mice parallels the timing of FGFR2-related craniosynostosis onset in humans, underscoring the importance of this study in advancing our understanding of the molecular and cellular mechanisms in craniosynostosis. Our findings define a temporally regulated FGFR2-P38-retinoic acid signaling axis and highlight retinoic acid signaling as a promising therapeutic target in FGFR2 overactivation-related craniosynostosis. - Source: PubMed
Publication date: 2026/08/17
Gao LuChen PengFeng JifanGuo TingweiZhang MingyiHo Thach-VuChen Jian-FuChai Yang - To describe a cohort of fetuses with abnormal prenatal findings in whom exome sequencing (ES) identified genetic diagnoses that refined prognostic assessment and reduced prognostic uncertainty. - Source: PubMed
Publication date: 2026/08/16
Rips JonathanMor-Shaked HagarBirnbaum RivkaEilat AvitalGoldwicht NataliePorat ShayErlik UriBenyamini LilachDaum Hagit - KRAS mutations are a major driver of pancreatic ductal adenocarcinoma (PDAC). RASA2, a RAS GTPase-activating protein, modulates KRAS protein levels in wild-type contexts, suggesting it could play a potential role in PDAC. Here, we systematically investigated the biological function and molecular mechanisms of RASA2 in PDAC. Integrative analyses of multiple datasets and clinical samples demonstrated that RASA2 was consistently upregulated in KRAS-mutant PDAC and significantly associated with poor prognosis and metastatic progression. Gain- and loss-of-function studies revealed that RASA2 markedly enhanced PDAC cell migration and invasion in both KRAS-mutant and KRAS-wild-type models, suggesting that its pro-metastatic activity is largely independent of KRAS mutational status. Transcriptomic and mechanistic analyses revealed that RASA2 activated GLI1 through a TGFβ2-dependent, non-canonical Hedgehog pathway. Mechanistically, RASA2 interacted with RTF1 to promote H2BK120 ubiquitination at the TGFB2 promoter, thereby enhancing TGFβ2 transcription and activating downstream GLI1 signaling. Pharmacological inhibition of TGFβ signaling or genetic silencing of GLI1 effectively suppressed RASA2-driven migratory, invasive, and metastatic phenotypes in vitro and in vivo. Collectively, these findings reveal a mechanism by which RASA2-dependent epigenetic and transcriptional reprogramming promotes metastatic progression and nominate the RASA2- TGFβ2-GLI1 axis as a potential therapeutic target in PDAC. - Source: PubMed
Publication date: 2026/08/14
He TaochenChen QiangdaAn YanfeiXu ZhihangJiang ZhenlaiHan JiandeXie YuqiLi HanyuPang ChaoyuXu JiayiGan WeiWang HaiboJin YunWang WenquanWang Xu-AnWu WenchuanLou WenhuiYin HanlinPu NingLiu Liang