Characteristic defects in neural crest cell-specific Gαq/Gα11- and Gα12/Gα13-deficient mice

The endothelin/endothelin receptor system plays a critical role in the differentiation and terminal migration of particular neural crest cell subpopulations. Targeted deletion of the G-protein-coupled endothelin receptors ETA and ETB was shown to result in characteristic developmental defects of derivatives of cephalic and cardiac neural crest and of neural crest-derived melanocytes and enteric neurons, respectively. Since both endothelin receptors are coupled to G-proteins of the G(q)/G(11)- and G(12)/G(13)-families, we generated mouse lines lacking G alpha(q)/G alpha(11) or G alpha(12)/G alpha(13) in neural crest cells to study their roles in neural crest development. Mice lacking G alpha(q)/G alpha(11) in a neural crest cell-specific manner had craniofacial defects similar to those observed in mice lacking the ETA receptor or endothelin-1 (ET-1). However, in contrast to ET-1/ETA mutant animals, cardiac outflow tract morphology was intact. Surprisingly, neither G alpha(q)/G alpha(11) - nor G alpha 12/ G alpha(13)-deficient mice showed developmental defects seen in animals lacking either the ETB receptor or its ligand endothelin-3 (ET-3). Interestingly, G alpha(12)/G alpha(13) deficiency in neural crest cell-derived cardiac cells resulted in characteristic cardiac malformations. Our data show that G(q)/G(11)- but not G(12)/G(13)-mediated signaling processes mediate ET-1/ETA-dependent development of the cephalic neural crest. In contrast, ET-3/ETB-mediated development of neural crest-derived melanocytes and enteric neurons appears to involve G-proteins different from G(q)/G(11)/G(12)/G(13). (c) 2005 Elsevier Inc. All rights reserved.