Ventral Mesencephalon-Enriched Genes That Regulate the Development of Dopaminergic NeuronsIn Vivo

Abstract

Mesodiencephalic dopaminergic (mDA) neurons are critical for movement control and other physiological activities. However, the molecular mechanisms underlying their development are poorly understood. We aimed to establish the expression profiles of genes involved in this process and unravel genetic programs that control late development of mDA neurons. We compared genome-wide gene expression profiles of developing mouse ventral mesencephalon (VM) using microarrays. We identified a set of genes that show spatially and temporally restricted expression in the VM in an Ngn2 (neurogenin 2)-dependent manner and are potentially important for mDA neuron development. Functional analysis on mice lacking the VM-specific gene early B-cell factor 1 (Ebf1) revealed that Ebf1 is essential for the terminal migration of mDA neurons in the substantia nigra pars compacta. Thus, we identified a set of VM-enriched genes that are important for mDA neuron development. Our analysis also provides a genetic framework for further investigation of the molecular mechanisms mediating mDA neuron development.

Expression of ventral diencephalon‐enriched genes in zebrafish

“…From 72 hpf on, Id3 expression was gradually down regulated. This up-then-down trend of Id3 expression in zebrafish is consistent with that in mouse VM revealed in our previous microarray data (Yin et al, 2009). These data suggest that Id3 may play a role in early development of DA neurons.…”

“…Previously, we found that Fabp7, a fatty acid binding protein, was exclusively expressed in neuroepithelial cells in the VM of mouse embryos in addition to other brain regions (Yin et al, 2009). In zebrafish larvae, Fabp7 mRNA was found to be highly enriched in the hindbrain, especially rhombomere 4, and also diencephalon as well as in the eyes (Figs.…”

“…Eight genes including five transcription factors were selected from the pool of differentially expressed genes of developing ventral mesencephalon (Yin et al, 2009) for the study in zebrafish larvae. These genes were Id3, Ebf2, Ebf3, Iroquois related homeobox 1 (Irx1), Kruppel-like factor 7 (Klf7), stathmin-like 4 (Stmn4), mab-21-like 1 (Mab21l1), and fatty acid binding protein 7 (Fabp7).…”

“…In our previous study, gene expression profiles of DA neurons-enriched ventral mesencephalon in developing mouse embryos were established by using a genomewide gene expression microarray analysis. A set of genes that showed restricted expression in the ventral midbrain and may regulate mesencephalic DA neuron development were thus identified (Yin et al, 2009). These genes appeared to be expressed in an Ngn2-dependent manner, suggesting that they are potentially important for mesencephalic DA neuron development.…”

“…Moreover, the development of diencephalic DA neurons in zebrafish has been less well studied. In the present study, we investigated the expression pattern in zebrafish of eight genes that were selected from a pool of differentially expressed genes in mouse ventral mesencephalon (Yin et al, 2009). Among these genes, early B cell factor 2 (Ebf2), early B cell factor 3 (Ebf3), and DNA binding inhibitor 3 (Id3) were found to be expressed strictly in the diencephalon of zebrafish at early development, especially in the critical period of DA neuron development.…”