RESUMEN
Crossveinless-2 (Cv2), Twisted Gastrulation (Tsg) and Chordin (Chd) are components of an extracellular biochemical pathway that regulates Bone Morphogenetic Protein (BMP) activity during dorso-ventral patterning of Drosophila and Xenopus embryos, the formation of the fly wing, and mouse skeletogenesis. Because the nature of their genetic interactions remained untested in the mouse, we generated a null allele for Cv2 which was crossed to Tsg and Chd mutants to obtain Cv2; Tsg and Cv2; Chd compound mutants. We found that Cv2 is essential for skeletogenesis as its mutation caused the loss of multiple bone structures and posterior homeotic transformation of the last thoracic vertebra. During early vertebral development, Smad1 phosphorylation in the intervertebral region was decreased in the Cv2 mutant, even though CV2 protein is normally located in the future vertebral bodies. Because Cv2 mutation affects BMP signaling at a distance, this suggested that CV2 is involved in the localization of the BMP morphogenetic signal. Cv2 and Chd mutations did not interact significantly. However, mutation of Tsg was epistatic to all CV2 phenotypes. We propose a model in which CV2 and Tsg participate in the generation of a BMP signaling morphogenetic field during vertebral formation in which CV2 serves to concentrate diffusible Tsg/BMP4 complexes in the vertebral body cartilage.
Asunto(s)
Proteínas Morfogenéticas Óseas/metabolismo , Gastrulación , Proteínas/metabolismo , Columna Vertebral/metabolismo , Alelos , Animales , Tipificación del Cuerpo/genética , Proteína Morfogenética Ósea 4/fisiología , Proteínas Morfogenéticas Óseas/genética , Embrión de Mamíferos , Regulación del Desarrollo de la Expresión Génica , Inmunohistoquímica , Hibridación in Situ , Ratones , Modelos Biológicos , Mutación , Proteínas/genética , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Like animals, plants use asymmetric cell divisions to create pattern and diversity. Due to a rigid cell wall and lack of cell migrations, these asymmetric divisions incur the additional constraints of being locked into their initial orientations. How do plants specify and carry out asymmetric divisions? Intercellular communication has been suspected for some time and recent developments identify these signals as well as point to segregated determinants and proteins with PAR-like functions as parts of the answer.
RESUMEN
Vertebrate Crossveinless-2 (CV2) is a secreted protein that can potentiate or antagonize BMP signaling. Through embryological and biochemical experiments we find that: (1) CV2 functions as a BMP4 feedback inhibitor in ventral regions of the Xenopus embryo; (2) CV2 complexes with Twisted gastrulation and BMP4; (3) CV2 is not a substrate for tolloid proteinases; (4) CV2 binds to purified Chordin protein with high affinity (K(D) in the 1 nM range); (5) CV2 binds even more strongly to Chordin proteolytic fragments resulting from Tolloid digestion or to full-length Chordin/BMP complexes; (6) CV2 depletion causes the Xenopus embryo to become hypersensitive to the anti-BMP effects of Chordin overexpression or tolloid inhibition. We propose that the CV2/Chordin interaction may help coordinate BMP diffusion to the ventral side of the embryo, ensuring that BMPs liberated from Chordin inhibition by tolloid proteolysis cause peak signaling levels.