Mechanism of hyperthermia effects on CNS development: rostral gene expression domains remain, despite severe head truncation; and the hindbrain/otocyst relationship is altered.
To study the mechanism of hyperthermia on the development of the rostral neural tube, we used a model in which closely-staged presomite 9.5-day rat embryos were exposed in culture to 43 degrees C for 13 min, and then cultured further for 12-48 hr. This treatment had little effect on the development of the rest of the embryo, but resulted in a spectrum of brain defects, the most severe being a lack of all forebrain and midbrain structures. Whole-mount in situ hybridisation was used to monitor the expression domains of Otx2, Emx2, Krox20, and hoxb1. These showed that there were no ectopic expression patterns, for any gene at any stage examined. Even in those embryos which apparently lacked all forebrain and midbrain structures, there were expression domains of Otx2 and Emx2 in the most rostral neural tissue, and these retained their nested dorso-ventral boundaries, showing that cells fated to form rostral brain were not wholly eliminated. Thus, heat-induced rostral neural tube truncation is of a quite different mechanism from the respecification proposed for retinoic acid, despite their very similar phenotypes. In the hindbrain region of treated embryos, we observed decreased intensity of Krox20, staining and an abnormal relationship developed between the position of hoxb1 expression and the otocyst and pharyngeal arches. In the most extreme cases, this domain was shifted to be more caudal than the rostral edge of the otocyst, while the otocyst retained its normal position relative to the pharyngeal arches. We interpret this as a growth imbalance between neuroepithelium and overlying tissues, perhaps due to a disruption of signals from the midbrain/hindbrain boundary.
Buckiová
D
D
Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague. bucki@biomed.cas.cz
Brown
N A
NA
D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000196:embryology; D002490:Central Nervous System / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D046508:Culture Techniques; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D006358:Hot Temperature; D017403:In Situ Hybridization; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012249:Rhombencephalon / Q000196:embryology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics
D014157:Transcription Factors