TSHZ1-dependent gene regulation is essential for olfactory bulb development and olfaction
| العنوان: | TSHZ1-dependent gene regulation is essential for olfactory bulb development and olfaction |
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| المؤلفون: | Ilse Feenstra, Elena Rocca, Anne M.M. Oonk, Alistair N. Garratt, Elvira Rohde, Ronald J.E. Pennings, Hagen Wende, Daniela Ragancokova, Jan Bednarsch, Herbert Schulz |
| المصدر: | Journal of Clinical Investigation, 124, 3, pp. 1214-27 Journal of Clinical Investigation, 124, 1214-27 |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Olfactory system, Male, PAX6 Transcription Factor, Rostral migratory stream, Kallmann syndrome, Gene Expression, Sensory disorders Radboud Institute for Health Sciences [Radboudumc 12], Receptors, G-Protein-Coupled, Mice, Cell Movement, Paired Box Transcription Factors, Child, Neurons, Gene Expression Regulation, Developmental, Cell Differentiation, Ear, General Medicine, Olfactory Bulb, Cell biology, Smell, medicine.anatomical_structure, Female, medicine.symptom, Function and Dysfunction of the Nervous System, Research Article, Adult, medicine.medical_specialty, Adolescent, Receptors, Peptide, Neurogenesis, Anosmia, Mice, Transgenic, Olfaction, Biology, Congenital Abnormalities, Internal medicine, medicine, Animals, Humans, Eye Proteins, Sensory disorders Radboud Institute for Molecular Life Sciences [Radboudumc 12], Genetic Association Studies, Homeodomain Proteins, Prokineticin receptor 2, Kallmann Syndrome, medicine.disease, Olfactory bulb, Repressor Proteins, Endocrinology, Gene Expression Regulation, Cardiovascular and Metabolic Diseases, Case-Control Studies, Transcriptome, Olfactory epithelium |
| الوصف: | Contains fulltext : 136916.pdf (Publisher’s version ) (Open Access) The olfactory bulb (OB) receives odor information from the olfactory epithelium and relays this to the olfactory cortex. Using a mouse model, we found that development and maturation of OB interneurons depends on the zinc finger homeodomain factor teashirt zinc finger family member 1 (TSHZ1). In mice lacking TSHZ1, neuroblasts exhibited a normal tangential migration to the OB; however, upon arrival to the OB, the neuroblasts were distributed aberrantly within the radial dimension, and many immature neuroblasts failed to exit the rostral migratory stream. Conditional deletion of Tshz1 in mice resulted in OB hypoplasia and severe olfactory deficits. We therefore investigated olfaction in human subjects from families with congenital aural atresia that were heterozygous for TSHZ1 loss-of-function mutations. These individuals displayed hyposmia, which is characterized by impaired odor discrimination and reduced olfactory sensitivity. Microarray analysis, in situ hybridization, and ChIP revealed that TSHZ1 bound to and regulated expression of the gene encoding prokineticin receptor 2 (PROKR2), a G protein-coupled receptor essential for OB development. Mutations in PROKR2 lead to Kallmann syndrome, characterized by anosmia and hypogonadotrophic hypogonadism. Our data indicate that TSHZ1 is a key regulator of mammalian OB development and function and controls the expression of molecules involved in human Kallmann syndrome. |
| وصف الملف: | application/pdf |
| تدمد: | 0021-9738 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a201930e71e168377ab9d9771ac402d5Test https://hdl.handle.net/2066/136916Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a201930e71e168377ab9d9771ac402d5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219738 |
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