THE TRH NEURONAL PHENOTYPE FORMS EMBRYONIC-CELL CLUSTERS THAT GO ON TO ESTABLISH A REGIONALIZED CELL FATE IN FOREBRAIN

How neurons diversify in developing brain to produce discrete cell fat es in their appropriate regions remains a fundamental question. Embryo nic Xenopus was previously used to identify juxtaposed embryonic cells that first express proopiomelanocortin mRNA in forebrain and pituitar y, supporting the idea that this neuropeptide phenotype is induced loc ally (Hayes and Loh, 1990, Development 110: 747-757). To begin to exam ine how a more widespread population of forebrain cells is set up, the present focus is on the thyrotropin-releasing hormone (TRH) phenotype . Serial section in situ hybridization histochemistry produced the une xpected finding that the adult-like TRH system spanning forebrain and comprising over six different telencephalic and diencephalic nuclei, i s preceded by an embryonic TRH cell population that is initially local ized and then highly regionalized in the area from which the adult pat tern develops. Thus, the first TRH cells, detected in vivo after 35 h (stage 29/30), were confined to discrete anterior or posterior bilater al clusters in embryonic forebrain or hindbrain. Thereafter, the TRH c ell clusters in diencephalon, but not hindbrain, expanded to form rows , extending anteriorly into telencephalon and bifurcating posteriorly around the infundibulum. By 80 h (stage 42), after extensive brain mor phogenesis, these forebrain rows showed regional differences in levels of TRH mRNA corresponding to the specific brain nuclei that have been shown to contain TRH cells in adult. These findings show that subsets of phenotype-specific forebrain cells first form a regionalized neuro nal cell fate before distinct brain nuclei form. This in turn points t o the testable hypothesis in Xenopus that certain neuronal cell fates in forebrain may be dictated by cell lineage or local induction. (C) 1 994 John Wiley and Sons, Inc.