Serotonin receptor 2

DEVELOPMENTAL BIOLOGY

Embryonic

The 5-HT2 mRNA is first detected by in situ hybridization on whole-mount embryos at the beginning of the cellular blastoderm stage (stage 6; 2 hr 50 min of development). This detection revealed seven evenly spaced transverse stripes along the anteroposterior axis of the embryo, a pattern similar to that of the pair-rule genes. Syncytial expression is not detectable, but the striped pattern appears before cephalic furrow formation, at the onset of cellularization. It is restricted to the ectodermal layer of the blastoderm embryo in four-cell-wide stripes, with uneven intensity among each parasegment. The seven stripes persist during germ-band extension and then the expression disappears. The 5-HT2 mRNA stripes are in phase with those of cells expressing the pair-rule gene fushi tarazu. The colocalization of the earliest-appearing stripe of en-expressing cells with the anterior margin of the most anterior 5-HT2 stripe locates the second parasegment and therefore confirms the 5-HT2 phasing with ftz in the even-numbered parasegments. Concomitant with the peak of 5-HT2 mRNA expression, peak amounts of specific 5-HT2 receptor binding sites and ligand are detected in blastoderm embryos. 5-HT2 mRNA reappears in the embryo ventral nerve cord as well as in the larval CNS in a pair of cells per neuromere, starting at stage 13 (Colas, 1995).

Effects of Mutation or Deletion

Embryos lacking the 5-HT2 locus show abnormal germband extension movements. In embryos bearing a deficiency in the 5-HT2 locus [Df(3R)HTRI], time-lapse video recordings reveal an apparently correct cellularisation and stage 6 progression: The cephalic furrow forms and both the mesoderm and the proctodeum start to invaginate. The germband initially extends dorsally in response to the pull from the endoderm primordium on the dorsal side of the embryo. However, in homozygous Df(3R)HTRI embryos (genotyped after recording), the extension movements become rapidly delayed. The rapid phase of germband extension, in 5-HT2 null embryos, occurs but at a clearly reduced speed. In the control embryos, cells at the anterior part of the germband, initially move both ventrally and anteriorly, pushing against the head region, which, by resisting, induces a bending of the cephalic furrow in the ventral region before disappearing. In contrast, in the deficient embryos the cephalic furrow remains roughly straight and visible for most of the rapid phase of germband extension suggesting that the pushing force is impaired or lacking. This absence of a pushing force is also evident later when extension is almost completely abolished in homozygous embryos. Using image analysis of the digital video recording, the speed of cell movements, near the ventral and dorsal midline of the embryo, was assessed. This was made possible by using newly developed software that allows the 'peeling off' of a superficial layer of the embryos in the video images, laying the embryo flat, and accumulating these images over time. This allows the quantification of the speed and extent of individual cell movement at the surface of an embryo and the evaluation of the synchronization of these movements (Colas, 1999a).

Taking the initiation of ventral extension movements as a reference time point, the reduced speed of the extension movements appears clearly in 5-HT2 null embryos at stage 7. After a short phase of contraction that corresponds to mesodermal cell shape changes and invagination (210 min) and to the posterior midgut dorsal shift, the ventral extension movements appear reduced both in the initial forward movements and in all the subsequent backward movements. Only the endoderm invagination movement occurs at approximately normal speed (10mm/min vs. 15 mm/min). The ectodermal cells move at a speed close to that observed after 20 min of germband extension in control embryos (about 4±5 mm/min). The pole cells invaginate about 3 min late and are not centered. These observations suggest that for mutant embryos, the dorsal contraction is not relayed properly by intercalation, the movements appearing slower, delayed and ending prematurely. The resulting effect is desynchronisation between germband extension and mesodermal and endodermal invaginations and a premature termination of movements (Colas, 1999a).

Signs of desynchronization can be visualized by scanning electron microscopy (SEM). In stage-7 embryos, the pole cells, rather than being centered in the forming proctodeal invagination, are located posteriorly, suggesting an impairment of support cell movements dependent on the ectoderm. Extreme desynchronization leading to a complete morphogenetic block is illustrated in older homozygous embryos. Here, elongated amnioserosa cells (typical of stage 8±9) fill an abnormally large dorsal gap between the front of the germband and the cephalic furrow, whereas pole cells are still visible outside and posterior to the internalised proctodeal invagination. Although in Df(3R)HTRI homozygous deficient embryos the mesoderm invagination is apparently normal, defects in the ventral midline closure are frequently observed (Colas, 1999a).

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date revised: 20 February 2007

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