Gain of affinity point mutation in the serotonin receptor gene 5‐HT_2Dro accelerates germband extension movements during Drosophila gastrulation

Abstract

Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morphogenetic factor during early embryogenesis. In Drosophila, a previous report showed that embryos that lack the 5-HT 2Dro receptor locus, display abnormal gastrulation movements. In this work, we screened for point mutations in the 5-HT 2Dro receptor gene. We identified one point mutation that generates a gain of serotonin affinity for the receptor and affects germband extension: 5-HT 2Dro C1644 . Embryos homozygous for this point mutation display a fourfold increase in the maximal speed of ectodermal cell movements during the rapid phase of germband extension. Homozygous 5-HT 2Dro C1644 embryos present a cuticular phenotype, including a total lack of denticle belt. Identification of this gain of function mutation shows the participation of serotonin in the regulation of the cell speed movements during the germband extension and suggests a role of serotonin in the regulation of cuticular formation during early embryogenesis. Developmental Dynamics 236:991-999, 2007.

Dispensable, Redundant, Complementary, and Cooperative Roles of Dopamine, Octopamine, and Serotonin inDrosophila melanogaster

“…This result also suggests that the vesicular release of DA and 5-HT may be dispensable for larval development and adult survival under standard culture conditions, an observation that is surprising given the fundamental role of DA in many physiological processes and the lethal effects of genetic (pale) (Kobayashi et al 1995) or pharmacologic inhibition of tyrosine hydroxylase activity (Neckameyer 1996;Pendleton et al 1996). Similarly, it has been proposed that 5-HT has a critical role in fly development (Colas et al 1999;Sykes and Condron 2005;Willard et al 2006;Schaerlinger et al 2007). In contrast to these results, it has been shown that mutants of aromatic L-amino acid decarboxylase/Dopa decarboxylase (AADC/DDC)-which converts 5-hydroxy-Ltryptophan (5-HTP) to 5-HT (Hodgetts and O'Keefe 2006)-and flies with increased or decreased 5-HT survive beyond third-instar larval stages (Budnik et al 1986;Sykes and Condron 2005;Neckameyer 2010).…”

“…the severe developmental phenotype of the 5HT2Dro mutant may reflect a requirement for nonvesicular release of 5-HT (Schaerlinger et al 2007). In addition, consistent with Riemensperger et al (2011), we find that the neuronal storage and exocytotic release of DA are not required for development.…”

Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster

“…For this receptor, two variants have been described. Either a point mutation changing Pro 52 to Ser in the N-terminus (Schaerlinger et al, 2007) or the complete deletion of the N-terminal domain leads to a significant gain of the receptor’s affinity for serotonin (Colas et al, 1997) compared to the wild type protein. Orthologous receptors to Dm5-HT 2A and Dm5-HT 2B have been characterized from other insects as well.…”

Drosophila Vesicular Monoamine Transporter Mutants Can Adapt to Reduced or Eliminated Vesicular Stores of Dopamine and Serotonin

“…The genetic rescue of dVMAT mutants using this driver therefore suggests the possibility that serotonergic neurotransmission might not be required for either development or survival. A large deletion that includes a serotonin receptor gene is embryonic lethal, and the analysis of an additional point mutant suggests that serotonin is required for gastrulation (Colas et al 1999;Schaerlinger et al 2007). Similarly, pharmacological experiments indicate a role for serotonin in oogenesis (Willard et al 2006).…”

“…Octopamine, which is structurally similar to noradrenaline, is involved in larval locomotion (Saraswati et al 2004;Fox et al 2006) and adult fertility (Monastirioti et al 1996;Cole et al 2005;Middleton et al 2006). Many components of the aminergic signaling machinery responsible for these behaviors are evolutionarily conserved (Morgan et al 1986;Budnik and White 1987;Konrad and Marsh 1987;Neckameyer and White 1993;Corey et al 1994;Demchyshyn et al 1994;Porzgen et al 2001;Yuan et al 2006;Draper et al 2007;Schaerlinger et al 2007); the behavioral responses of flies and humans to psychostimulants are also similar (McClung and Hirsh 1998;Bainton et al 2000;Andretic et al 2005). These similarities suggest that D. melanogaster may be used as a genetic model to study the molecular mechanisms by which amines regulate synaptic transmission and behavior.…”