Serotonin has early, cilia-independent roles in Xenopus left-right patterning.
Consistent left-right (LR) patterning of the heart and viscera is a crucial part of normal embryogenesis. Because errors of laterality form a common class of birth defects, it is important to understand the molecular mechanisms and stage at which LR asymmetry is initiated. Frog embryos are a system uniquely suited to analysis of the mechanisms involved in orientation of the LR axis because of the many genetic and pharmacological tools available for use and the fate-map and accessibility of early blastomeres. Two major models exist for the origin of LR asymmetry and both implicate pre-nervous serotonergic signaling. In the first, the charged serotonin molecule is instructive for LR patterning; it is redistributed asymmetrically along the LR axis and signals intracellularly on the right side at cleavage stages. A second model suggests that serotonin is a permissive factor required to specify the dorsal region of the embryo containing chiral cilia that generate asymmetric fluid flow during neurulation, a much later process. We performed theory-neutral experiments designed to distinguish between these models. The results uniformly support a role for serotonin in the cleavage-stage embryo, long before the appearance of cilia, in ventral right blastomeres that do not contribute to the ciliated organ.
Center for Regenerative and Developmental Biology and Department of Biology, Tufts University, 200 Boston Avenue, Suite 4600, Medford, MA 02155, USA.
Laura N
LN
Vandenberg
Joan M
JM
Lemire
Michael
M
Levin
D000818:Animals; D001757:Blastomeres / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019521:Body Patterning / Q000187:drug effects / Q000502:physiology*; D002923:Cilia / Q000502:physiology; D002970:Cleavage Stage, Ovum / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D023421:Models, Animal; D008954:Models, Biological; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology*
D012702:Serotonin Antagonists; D029867:Xenopus Proteins; C512833:nodal1 protein, Xenopus; D012701:Serotonin