Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016632 (Fox)
1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoic acid regulates development of many chordate-specific characteristics. The genes encoding retinoic acid receptors (RARs) were isolated only from chordates. In the present study, a genomic DNA fragment containing the promoter region of the RAR gene (Ci-RAR) in the protochordate Ciona intestinalis was isolated. The transgene containing 1,326 bp of the Ci-RAR 5' flanking region was expressed in the epidermis, central nervous system, and muscle. The sequence element necessary for expression in the epidermis seemed to be subdivided into two elements. One was required for activation in the dorsal midline epidermis and the other for the rest of the epidermis. The element responsible for activation in the central nervous system was characterized by putative binding sites for Fox, Ets, and GATA transcription factors. An E-box sequence was required for the transgene expression in the tail muscle cells.
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PMID:Promoter activity of the retinoic acid receptor gene in the Ciona intestinalis embryo. 1573 69

Retinoic acid (RA) is essential during embryogenesis and for tissue homeostasis, whereas excess RA is well known as a teratogen. In humans, excess RA is associated with hair loss. In the present study, we demonstrate that specific levels of RA, regulated by Cyp26b1, one of the RA-degrading enzymes, are required for hair follicle (hf) morphogenesis. Mice with embryonic ablation of Cyp26b1 (Cyp26b1(-/-)) have excessive endogenous RA, resulting in arrest of hf growth at the hair germ stage. The altered hf development is rescued by grafting the mutant skin on immunodeficient mice. Our results show that normalization of RA levels is associated with reinitiation of hf development. Conditional deficiency of Cyp26b1 in the dermis (En1Cre;Cyp26b1f/-) results in decreased hair follicle density and specific effect on hair type, indicating that RA levels also influence regulators of hair bending. Our results support the model of RA-dependent dermal signals regulating hf downgrowth and bending. To elucidate target gene pathways of RA, we performed microarray and RNA-Seq profiling of genes differentially expressed in Cyp26b1(-/-) skin and En1Cre;Cyp26b1f/- tissues. We show specific effects on the Wnt-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families, indicating that RA modulates pathways and factors implicated in hf downgrowth and bending. Our results establish that proper RA distribution is essential for morphogenesis, development, and differentiation of hfs.
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PMID:Cutaneous retinoic acid levels determine hair follicle development and downgrowth. 2300 96