ArticleHuman molecular genetics2015
Deletion of OTX2 in neural ectoderm delays anterior pituitary development.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Human Pituitary Organoids: Transcriptional Landscape Deciphered by scRNA-Seq and Stereo-Seq, with Insights into SOX3's Role in Pituitary Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pituitary stem cells: past, present and future perspectives.Nature reviews. Endocrinology · 2024Review
- Comprehensive transcriptomic analysis revealing the regulatory dynamics and networks of the pituitary-testis axis in sheep across developmental stages.Frontiers in veterinary science · 2024Article
- Cortical interneuron development is affected in 4H leukodystrophy.Brain : a journal of neurology · 2023Article
- c-Jun N-terminal kinase 1 (JNK1) phosphorylates OTX2 transcription factor that regulates early retinal development.Genes & genomics · 2023Article
- Phospho-seq: Integrated, multi-modal profiling of intracellular protein dynamics in single cells.bioRxiv : the preprint server for biology · 2023Article
- Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.Human molecular genetics · 2023Article
- Organoid models of the pituitary gland in health and disease.Frontiers in endocrinology · 2023Review
- Single-Step Genome Editing of Small Ruminant Embryos by Electroporation.International journal of molecular sciences · 2022Article
- DNA methylation biomarkers in asthma and rhinitis: Are we there yet?Clinical and translational allergy · 2022Review
- Region Specific Brain Organoids to Study Neurodevelopmental Disorders.International journal of stem cells · 2022Review
- Genetic Regulation of Vertebrate Forebrain Development by Homeobox Genes.Frontiers in neuroscience · 2022Review
- Neonatal Porcine Germ Cells Dedifferentiate and Display Osteogenic and Pluripotency Properties.Cells · 2021Article
- Pituitary Tumors and Immortalized Cell Lines Generated by Cre-Inducible Expression of SV40 T Antigen.Endocrinology · 2021Article
- The phenotypic spectrum associated with OTX2 mutations in humans.European journal of endocrinology · 2021Article
- Multi-omic profiling of pituitary thyrotropic cells and progenitors.BMC biology · 2021Article
- Human pituitary development and application of iPSCs for pituitary disease.Cellular and molecular life sciences : CMLS · 2021Review
- IFI16 promotes human embryonic stem cell trilineage specification through interaction with p53.NPJ Regenerative medicine · 2020Article
- Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development.Nature communications · 2020Article
- Otx2b mutant zebrafish have pituitary, eye and mandible defects that model mammalian disease.Human molecular genetics · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
OTX2 is a homeodomain transcription factor that is necessary for normal head development in mouse and man. Heterozygosity for loss-of-function alleles causes an incompletely penetrant, haploinsufficiency disorder. Affected individuals exhibit a spectrum of features that range from developmental defects in eye and/or pituitary development to acephaly. To investigate the mechanism underlying the pituitary defects, we used different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. Mice homozygous for Otx2 deficiency in early head development and pituitary oral ectoderm exhibit craniofacial defects and pituitary gland dysmorphology, but normal pituitary cell specification. The morphological defects mimic those observed in humans and mice with OTX2 heterozygous mutations. Mice homozygous for Otx2 deficiency in the pituitary neural ectoderm exhibited altered patterning of gene expression and ablation of FGF signaling. The posterior pituitary lobe and stalk, which normally arise from neural ectoderm, were extremely hypoplastic. Otx2 expression was intact in Rathke's pouch, the precursor to the anterior lobe, but the anterior lobe was hypoplastic. The lack of FGF signaling from the neural ectoderm was sufficient to impair anterior lobe growth, but not the differentiation of hormone-producing cells. This study demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe and pituitary stalk, and it has significant extrinsic effects on anterior pituitary growth. Otx2 expression early in head development is important for establishing normal craniofacial features including development of the brain, eyes and pituitary gland.
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Registered trials
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