title: Thyroid hormone and retinoic acid interact to regulate zebrafish craniofacial neural crest development.
abstract: Craniofacial and ocular morphogenesis require proper regulation of cranial neural crest migration, proliferation, survival and differentiation. Although alterations in maternal thyroid hormone (TH) are associated with congenital craniofacial anomalies, the role of TH on the neural crest has not been previously described. Using zebrafish, we demonstrate that pharmacologic and genetic alterations in TH signaling disrupt cranial neural crest migration, proliferation, and survival, leading to craniofacial, extraocular muscle, and ocular developmental abnormalities. In the rostral cranial neural crest that gives rise to the periocular mesenchyme and the frontonasal process, retinoic acid (RA) rescued migratory defects induced by decreased TH signaling. In the caudal cranial neural crest, TH and RA had reciprocal effects on anterior and posterior pharyngeal arch development. The interactions between TH and RA signaling were partially mediated by the retinoid X receptor. We conclude that TH regulates both rostral and caudal cranial neural crest. Further, coordinated interactions of TH and RA are required for proper craniofacial and ocular development.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Bohnsack
authors.forename: Alon
authors.initials: A
authors.lastname: Kahana
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005123:Eye / Q000187:drug effects / Q000196:embryology; D005145:Face / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D008954:Models, Biological; D024510:Muscle Development / Q000187:drug effects; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000187:drug effects / Q000196:embryology*; D013963:Thyroid Hormones / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D013956:Antithyroid Agents; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D029961:Zebrafish Proteins; D014212:Tretinoin