mPet-1, a mouse ETS-domain transcription factor, is expressed in central serotonergic neurons

Abstract

Here we describe the expression pattern of a previously unknown mouse gene mPet-1. The isolated cDNA codes for an ETS-domain transcription factor of 237 amino acids in length, which is localized to the nucleus. mPet-1 is a member of the winged helix transcription factor gene family like its rat homologue Pet-1 and the human homologue FEV. The start ATG of mPet-1 and the size of the predicted protein are identical to the human FEV. The mPet-1 protein is clearly smaller since it lacks the first 103 N-terminal amino acids of rat Pet-1. mPet- 1 is expressed in central serotonergic (5-hydroxytryptaminergic) neurons located in the mes-/metencephalic raphe nuclei from E11 on until adulthood. In these regions mPet-1 expression co-localizes precisely with the serotonin transporter (Sert),which it initially precedes. Interestingly, mPet-1 was not found in neurons transiently expressing Sert.

The serotonergic phenotype is acquired by converging genetic mechanisms within the zebrafish central nervous system

“…The Ets family contains some 30 different members, of which Erg and Fli-1 are most closely related to Pet-1. In the present study, we have identified one zebrafish homologue of Pet-1 showing 89% identity to mouse Pet-1 within the Ets domain (Pfaar et al, 2002). As reported for mammals (Peter et al, 1997;Fyodorov et al, 1998;Pfaar et al, 2002), the main form of zebrafish Pet1 is encoded by three exons.…”

“…In the present study, we have identified one zebrafish homologue of Pet-1 showing 89% identity to mouse Pet-1 within the Ets domain (Pfaar et al, 2002). As reported for mammals (Peter et al, 1997;Fyodorov et al, 1998;Pfaar et al, 2002), the main form of zebrafish Pet1 is encoded by three exons. However, we identified for this transcript 39 additional base pairs in the fish genome, giving rise to 13 additional N-terminal aa, which we could not find in other species by in silico search.…”

“…Previous studies of chicken, mouse, rat, and human have identified Pet-1/ FEV as a specific marker for postmitotic raphe serotonergic neurons preceding the expression of serotonergic neuron-specific proteins such as Tph and Sert (Hendricks et al, 1999;Pfaar et al, 2002;Craven et al, 2004;Maurer et al, 2004). Our findings that pet1 has a similar expression pattern as tph2 in the hindbrain during embryonic, larval, and adult stages, suggests that pet1 is also a valid marker for this specific cell population in zebrafish.…”

“…To identify the origin of anterior raphe 5HT neurons in zebrafish, and to start analyzing the 5HT regulatory cascade in this species, we cloned the zebrafish homologue of mouse Pet-1 (Pfaar et al, 2002). We analyzed its temporal and spatial expression pattern during development and adulthood, thereby also verifying pet1 as a specific marker for anterior raphe serotonergic neurons in zebrafish.…”

A Differentially AutoregulatedPet-1Enhancer Region Is a Critical Target of the Transcriptional Cascade That Governs Serotonin Neuron Development

“…The onset of Pet-1 expression in the mouse brain occurs at approximately embryonic day 11 (E11) in postmitotic precursors within the mantle layer (Pfaar et al, 2002;Pattyn et al, 2003). Expression is restricted to two bilateral longitudinal hindbrain domains at the level of rhombomeres r1-r3 and r5-r8.…”