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)

Forkhead transcription factor (Fox) e1 is a causative gene for Bamforth-Lazarus syndrome, which is characterized by hypothyroidism and cleft palate. Applying degenerate polymerase chain reaction using primers specific for the conserved forkhead domain, we identified zebrafish foxe1 (foxe1). Foxe1 is expressed in the thyroid, pharynx, and pharyngeal skeleton during development; strongly expressed in the gill and weakly expressed in the brain, eye, and heart in adult zebrafish. A loss of function of foxe1 by morpholino antisense oligo (MO) exhibited abnormal craniofacial development, shortening of Meckel's cartilage and the ceratohyals, and suppressed chondrycytic proliferation. However, at 27 hr post fertilization, the foxe1 MO-injected embryos showed normal dlx2, hoxa2, and hoxb2 expression, suggesting that the initial steps of pharyngeal skeletal development, including neural crest migration and specification of the pharyngeal arch occurred normally. In contrast, at 2 dpf, a severe reduction in the expression of sox9a, colIIaI, and runx2b, which play roles in chondrocytic proliferation and differentiation, was observed. Interestingly, fgfr2 was strongly upregulated in the branchial arches of the foxe1 MO-injected embryos. Unlike Foxe1-null mice, normal thyroid development in terms of morphology and thyroid-specific marker expression was observed in foxe1 MO-injected zebrafish embryos. Taken together, our results indicate that Foxe1 plays an important role in chondrogenesis during development of the pharyngeal skeleton in zebrafish, probably through regulation of fgfr2 expression. Furthermore, the roles reported for FOXE1 in mammalian thyroid development may have been acquired during evolution.
 ...
PMID:Forkhead transcription factor foxe1 regulates chondrogenesis in zebrafish. 1948 87

Cleft palate is a common birth defect that frequently occurs in human congenital malformations caused by mutations in components of the Sonic Hedgehog (S HH) signaling cascade. Shh is expressed in dynamic, spatiotemporal domains within epithelial rugae and plays a key role in driving epithelial-mesenchymal interactions that are central to development of the secondary palate. However, the gene regulatory networks downstream of Hedgehog (Hh) signaling are incompletely characterized. Here, we show that ectopic Hh signaling in the palatal mesenchyme disrupts oral-nasal patterning of the neural crest cell-derived ectomesenchyme of the palatal shelves, leading to defective palatine bone formation and fully penetrant cleft palate. We show that a series of Fox transcription factors, including the novel direct target Foxl1, function downstream of Hh signaling in the secondary palate. Furthermore, we demonstrate that Wnt/bone morphogenetic protein (BMP) antagonists, in particular Sostdc1, are positively regulated by Hh signaling, concomitant with downregulation of key regulators of osteogenesis and BMP signaling effectors. Our data demonstrate that ectopic Hh-Smo signaling downregulates Wnt/BMP pathways, at least in part by upregulating Sostdc1, resulting in cleft palate and defective osteogenesis.
 ...
PMID:Ectopic Hedgehog Signaling Causes Cleft Palate and Defective Osteogenesis. 2997 48