Serotonin, expression

Heils, A., Teufel, A., Petri, S. etal. (1996). Allelic variation ofhuman serotonin transporter gene expression. /. Neurochem., 66, 2621M. 

Monsma, F.J. Jr, Shen, Y., Ward, R. P., Hamblin, M.W. 8c Sibley, D. R. (1993). Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol. Pharmacol., 43, 320-7. 

Ramamoorthy, S., Bauman, A. L., Moore, K. R. et al. (1993). Antidepressants- and cocaine-sensitive human serotonin transporter molecular cloning, expression, and chromosomal localization. Proc. Natl. Acad. Sci. USA, 90, 2542-6. 

Drosophila Ddc is expressed primarily in the CNS and the hypoderm, the epithelial layer of the fly that secretes the cuticle. In the CNS, Ddc is expressed in a small subset of neurons that produce either dopamine or serotonin (Budnik and White, 1988 Valles and White, 1988). In the hypoderm, Ddc expression leads to synthesis of dopamine, which is further metabolized into quinones that have a vital function in the cross-linking, hardening, and pigmentation of the fly cuticle (Wright, 1987). The developmental profile of DDC activity in these two tissues is quite different (Hirsh, 1986). DDC is first detected during late embryo-... 

Figure 3. Sketch of DDC-expressing neurons in the Drosophila larval CNS. The CNS consists of brain lobes and a segmented ventral ganglion. Filled circles represent dopamine cells open circles represent serotonin cells grayed circles represent DDC cells that contain no detectable tyrosine hydroxylase or serotonin immunoreactivity, indicating that these cells may produce neither transmitter (Lundell and Hirsh, 1994). M, medial dopamine neurons VL, ventrolateral serotonin neurons DL, dorsolateral dopamine neurons. The hatched rectangle shows the region of the ventral ganglion that is shown in Figures 4 and 6.

The majority of DDC-expressing cells in the brain lobes are dopamine cells. Most of these dopamine cells have axons that project into a common axonal fiber extending anteriomedially within the brain lobe and then separating into finer fibers that cross between the lobes. The dopamine cells occur in small clusters of two to six cells, which suggests that these cells might share common lineages. The serotonin cells within the lobes are also found in pairs, and each pair projects axons into closely associated tracts. The pathways of the serotonin tracts often parallel those of the dopamine cells but are distinct (Lundell and Hirsh, 1994). 

Figure 4 shows confocal images of the staining pattern for DDC (Fig. 4A), serotonin (Fig. 4B), and TH (Fig. 4C) in the segmental ventral ganglion of the CNS from third instar larvae. Panels B and C are the same CNS double stained with serotonin and TH. The DDC-expressing cells can be categorized into a set of paired ventral lateral serotonin cells (Fig. 4A,B labeled VL in 4A), and two morphologically distinct types of dopamine cells, the medial dopamine cells (Fig. 4A,C labeled M) and the dorsal-lateral dopamine cells (Fig. 4A,C labeled DL). Figure 4 demonstrates clearly that individual DDC cells synthesize either serotonin or dopamine, but not both. One additional set of cells shows TH immunoreactivity in the ventral ganglion. These six large vacuolated cells are located more laterally than any other DDC cells (Fig. 4C, unlabeled short arrows). It is likely that the immunoreactivity in these cells results from a non-specific cross-reaction, since these cells are not...

The axonal projections from the DDC-expressing cells in the ventral ganglion also show tendencies to follow common pathways. The projections from the ventral lateral serotonin cells extend medially to fuse with axons projecting from the contralateral serotonin cells. At the midline, this projection is met by an axonal projection from the medial dopamine cell. 

The second cell-specific regulatory element within the distal enhancer is named SER. Loss of this element, which is at the extreme distal edge of the enhancer, leads to a selective loss of DDC expression in the ventral lateral serotonin cells (Johnson et al., 1989 Lundell and Hirsh, 1992) (Fig. 6C). This element has been delimited to about 40 bp and shows unexpected complexity, consisting of two functionally redundant elements. These two subelements, SERl and SERr, are each sufficient to allow normal DDC expression in the ventral lateral serotonin neurons if the other is deleted. In spite of this functional similarity, no sequence similarity is apparent between the two regions. The region of conservation between D. melanogaster and D. virilis is limited to SERl. 

Figure 8. Colocalization of DDC and ZFH-2 in larval CNS. This figure shows abdominal segments 4-7 of a third instar larval CNS. DDC im-munoreactivity is cytoplasmic and is shown in red, whereas ZFH-2 im-munoreactivity is nuclear and is shown in green. Only the outside cell of each pair of serotonin neurons expresses ZFH-2. One medial dopamine cell shown at the top also shows ZFH-2 expression. This projection does not include the dorsolateral cells, which also express ZFH-2. A similar projection has been published in Lundell and Hirsh (1992).

The following references present work relevant to this manuscript that have been published since the time of submission. For a description on the embryonic developmental expression of DDC, TH, serotonin and dopamine see Lundell and Hirsh, 1994. For a more detailed examination of elements essential in the alternative splicing of Ddc see Shen et al., 1993 and Shen and Hirsh, 1994. For additional work on the use of gene transfection in the treatment of Parkinson s disease see Kang et al., 1993. 

Maricq, A. V., Peterson, A. S., Brake, A. J., Myers, R. M., and Julius, D. (1991). Primary structure and function expression of the 5HT3 receptor, a serotonin-gated ion channel. Science 254 432-437. 

Saudou, F., Boschert, U Amlaiky, N Plassat, J. L and Hen, R. (1992). A family of Drosophila serotonin receptors with distinct intracellular signalling properties and expression patterns. EMBO J. 11 7-17. 

Serrats, J., Mengod, G. Cortes, R. (2005). Expression of serotonin 5-HT2c receptors in GABAergic cells of the anterior raphe nuclei. J. Client. Neuroanat. 29,... 

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