Quantitative mRNA analysis of serotonin 5-HT₄ and adrenergic β₂ receptors in the mouse embryonic telencephalon.
The adrenergic β₂ receptor (β₂-AR) gene is embedded (nested) within the serotonin 5-HT₄ receptor (5-HT₄-R) gene and these two receptors can interact at the transcriptional and post-transcriptional levels. The mouse 5-HT₄-R gene contains a number of exons and codes at least four mRNA splice variants (5-HT(4(a))-R, 5-HT(4(b))-R, 5-HT(4(e))-R, 5-HT(4(f))-R), whereas the β₂-AR gene is intronless. Since 5-HT₄-Rs and β₂-ARs can form homodimers and heterodimers and they increase intracellular cAMP levels, these receptors may be important for integrating serotonergic and noradrenergic signals at the single-neuron level. Both 5-HT₄-R and β₂-AR have been implicated in autism spectrum disorders, depression, and Alzheimer's disease. In the fetal brain, these receptors may mediate the effects of stress on neurodevelopmental processes. We used quantitative reverse-transcription PCR (qRT-PCR) to investigate the developmental expression of 5-HT₄-R and β₂-AR in the mouse telencephalon at embryonic days (E) 13-18. At E13-E14, the mRNA levels of all 5-HT₄-R splice variants were very low, but by E17-E18 they increased 7-fold (5- HT(4(a))-R), 5-fold (5-HT(4(b))-R), 9-fold (5-HT(4(e))-R), and 11-fold (5-HT(4(f))-R). The expression of 5-HT(4(a))-R and 5-HT(4(b))-R was rapidly upregulated between E14 and E15, at the time when the thalamocortical projections arrive in the telencephalon. This pattern was not observed in the expression of 5-HT(4(e))-R and 5-HT(4(f))-R, the mRNA levels of which showed a steady, gradual increase from E13 to E18. The β₂-AR mRNA levels were relatively high throughout the studied period of development and increased only by 70% from E13-E14 to E17-E18. These findings suggest that 5-HT₄-R splice variants and β₂-ARs are differentially regulated in the embryonic telencephalon and that their relative amounts may carry developmentally important information.
Hernandez
Melissa C
MC
Department of Psychology, University of California, Santa Barbara, CA 93106-9660, USA.
Janušonis
Skirmantas
S
D000818:Animals; D004622:Embryo, Mammalian; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis*; D044422:Receptors, Serotonin, 5-HT4 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013687:Telencephalon / Q000378:metabolism*
D020033:Protein Isoforms; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D044422:Receptors, Serotonin, 5-HT4