PMID- 10359515 OWN - NLM STAT- MEDLINE DCOM- 19990617 LR - 20190122 IS - 0003-276X (Print) IS - 0003-276X (Linking) VI - 255 IP - 2 DP - 1999 Jun 1 TI - 13-cis-Retinoic acid alters neural crest cells expressing Krox-20 and Pax-2 in macaque embryos. PG - 142-54 AB - This study investigates hindbrain and associated neural crest (NCC), otocyst, and pharyngeal arch development in monkey embryos following teratogenic exposure to 13-cis-retinoic acid (cRA). cRA was orally administered (5 mg/kg) to pregnant long-tailed macaques (Macaca fascicularis) between gestational days (GD) 12 and 27. Embryos were surgically collected at desired stages during treatment, analyzed for external morphological changes, and processed for immunohistochemistry. Two transiently expressed nuclear proteins, Krox-20 and Pax-2, were used as markers for the target cellular and anatomical structures. Rhombomere (r) expression patterns of Pax-2 (r4/r6) and Krox-20 (r3/r5) were maintained after cRA treatment, but r4 and r5 were substantially reduced in size. In untreated embryos, Krox-20 immunoreactive NCC derived from r5 migrated caudally around the developing otocyst to contribute to the third pharyngeal arch mesenchyme. In cRA-treated embryos, a subpopulation of NCC rostral to the otocyst also showed Krox-20 immunoreactivity, but there was a substantial reduction in Krox-20 post-otic NCC. Pax-2 immunoreactive NCC migrating from r4 to the second pharyngeal arch were substantially reduced in numbers in treated embryos. Alteration in the otic anlage included delayed invagination, abnormal relationship with the adjacent hindbrain epithelium, and altered expression boundaries for Pax-2. cRA-associated changes in the pharyngeal arch region due to cRA included truncation of the distal portion of the first arch and reduction in the size of the second arch. These alterations in hindbrain, neural crest, otic anlage, and pharyngeal arch morphogenesis could contribute to some of the craniofacial malformations in the macaque fetus associated with exposure to cRA. FAU - Makori, N AU - Makori N AD - California Regional Primate Research Center, University of California, Davis 95616-8542, USA. FAU - Peterson, P E AU - Peterson PE FAU - Wei, X AU - Wei X FAU - Hummler, H AU - Hummler H FAU - Hendrickx, A G AU - Hendrickx AG LA - eng GR - RR00169/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Anat Rec JT - The Anatomical record JID - 0370540 RN - 0 (DNA-Binding Proteins) RN - 0 (Early Growth Response Protein 2) RN - 0 (PAX2 Transcription Factor) RN - 0 (Teratogens) RN - 0 (Transcription Factors) RN - EH28UP18IF (Isotretinoin) SB - IM MH - Animals MH - Branchial Region/drug effects/embryology/metabolism MH - Cochlea/drug effects/embryology/metabolism MH - DNA-Binding Proteins/*metabolism MH - Early Growth Response Protein 2 MH - Embryonic and Fetal Development/*drug effects MH - Female MH - Image Processing, Computer-Assisted MH - Immunoenzyme Techniques MH - Isotretinoin/*toxicity MH - Macaca mulatta MH - Neural Crest/*drug effects/embryology MH - PAX2 Transcription Factor MH - Pregnancy MH - Rhombencephalon/drug effects/embryology/metabolism MH - Teratogens/*toxicity MH - Transcription Factors/*metabolism EDAT- 1999/06/08 10:00 MHDA- 2000/06/20 09:00 CRDT- 1999/06/08 10:00 PHST- 1999/06/08 10:00 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1999/06/08 10:00 [entrez] AID - 10.1002/(SICI)1097-0185(19990601)255:2<142::AID-AR4>3.0.CO;2-D [pii] AID - 10.1002/(SICI)1097-0185(19990601)255:2<142::AID-AR4>3.0.CO;2-D [doi] PST - ppublish SO - Anat Rec. 1999 Jun 1;255(2):142-54. doi: 10.1002/(SICI)1097-0185(19990601)255:2<142::AID-AR4>3.0.CO;2-D.