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1.
Dev Biol ; 424(1): 28-39, 2017 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-28237811

RESUMEN

Wnt proteins are critical for embryonic cardiogenesis and cardiomyogenesis by regulating different intracellular signalling pathways. Whereas canonical Wnt/ß-catenin signalling is required for mesoderm induction and proliferation of cardiac progenitor cells, ß-catenin independent, non-canonical Wnt signalling regulates cardiac specification and terminal differentiation. Although the diverse cardiac malformations associated with the loss of non-canonical Wnt11 in mice such as outflow tract (OFT) defects, reduced ventricular trabeculation, myofibrillar disorganization and reduced cardiac marker gene expression are well described, the underlying molecular mechanisms are still not completely understood. Here we aimed to further characterize Wnt11 mediated signal transduction during vertebrate cardiogenesis. Using Xenopus as a model system, we show by loss of function and corresponding rescue experiments that the non-canonical Wnt signalling mediator Rcsd1 is required downstream of Wnt11 for ventricular trabeculation, terminal differentiation of cardiomyocytes and cardiac morphogenesis. We here place Rcsd1 downstream of Wnt11 during cardiac development thereby providing a novel mechanism for how non-canonical Wnt signalling regulates vertebrate cardiogenesis.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/metabolismo , Miocardio/metabolismo , Organogénesis , Proteínas Wnt/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/metabolismo , Secuencias de Aminoácidos , Animales , Diferenciación Celular , Citoplasma/metabolismo , Desarrollo Embrionario , Eliminación de Gen , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/química , Ratones , Miocardio/patología , Células 3T3 NIH , Fenotipo , Unión Proteica , Transducción de Señal , Proteínas de Xenopus/química
2.
Development ; 144(2): 321-333, 2017 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-27993984

RESUMEN

The signal-induced proliferation-associated family of proteins comprises four members, SIPA1 and SIPA1L1-3. Mutations of the human SIPA1L3 gene result in congenital cataracts. In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects. We found a direct interaction between Sipa1l3 and Epha4, building a functional platform for proper ocular development. Epha4 deficiency phenocopied loss of Sipa1l3 and rescue experiments demonstrated that Epha4 acts upstream of Sipa1l3 during eye development, with both Sipa1l3 and Epha4 required for early eye specification. The ocular phenotype, upon loss of either Epha4 or Sipa1l3, was partially mediated by rax We demonstrate that canonical Wnt signaling is inhibited downstream of Epha4 and Sipa1l3 during normal eye development. Depletion of either Sipa1l3 or Epha4 resulted in an upregulation of axin2 expression, a direct Wnt/ß-catenin target gene. In line with this, Sipa1l3 or Epha4 depletion could be rescued by blocking Wnt/ß-catenin or activating non-canonical Wnt signaling. We therefore conclude that this pathomechanism prevents proper eye development and maturation of lens fiber cells, resulting in congenital cataracts.


Asunto(s)
Ojo/embriología , Proteínas Activadoras de GTPasa/fisiología , Cristalino/embriología , Cristalino/crecimiento & desarrollo , Receptor EphA4/fisiología , Vía de Señalización Wnt/fisiología , Animales , Animales Modificados Genéticamente , Catarata/genética , Diferenciación Celular/genética , Embrión no Mamífero , Ojo/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Regulación del Desarrollo de la Expresión Génica , Humanos , Cristalino/metabolismo , Organogénesis/genética , Unión Proteica , Receptor EphA4/metabolismo , Xenopus/embriología , Xenopus/genética
3.
J Cardiovasc Dev Dis ; 3(2)2016 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-29367567

RESUMEN

The African clawed frog, Xenopus, is a valuable non-mammalian model organism to investigate vertebrate heart development and to explore the underlying molecular mechanisms of human congenital heart defects (CHDs). In this review, we outline the similarities between Xenopus and mammalian cardiogenesis, and provide an overview of well-studied cardiac genes in Xenopus, which have been associated with congenital heart conditions. Additionally, we highlight advantages of modeling candidate genes derived from genome wide association studies (GWAS) in Xenopus and discuss commonly used techniques.

4.
Int J Dev Biol ; 58(10-12): 841-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26154325

RESUMEN

Members of the cysteine-rich intestinal protein (Crip) family belong to the group 2 LIM proteins. Crip proteins are widely expressed in adult mammals but their expression profile and function during embryonic development are still mostly unknown. In this study, we have described for the first time the spatio-temporal expression pattern of the three family members crip1, crip2 and crip3 during Xenopus laevis embryogenesis by RT-PCR and whole mount in situ hybridization approaches. We observed that all three genes are expressed in the pronephros, branchial arches and the eye. Furthermore, crip1 transcripts could be visualized in the developing cranial ganglia and neural tube. In contrast, crip2 could be detected in the cardiovascular system, the brain and the neural tube while crip3 was expressed in the cranial ganglions and the heart. Based on these findings, we suggest that each crip family member may play an important role during embryonic development.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Regulación del Desarrollo de la Expresión Génica/genética , Proteínas con Dominio LIM/biosíntesis , Proteínas de Xenopus/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Encéfalo/metabolismo , Región Branquial/metabolismo , Sistema Cardiovascular/metabolismo , Embrión no Mamífero/metabolismo , Desarrollo Embrionario , Ojo/metabolismo , Ganglios/metabolismo , Hibridación in Situ , Proteínas con Dominio LIM/genética , Miocardio/metabolismo , Tubo Neural/metabolismo , Pronefro/metabolismo , Proteínas de Xenopus/genética , Xenopus laevis
5.
PLoS One ; 8(7): e69372, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23874955

RESUMEN

SoxC genes are involved in many developmental processes such as cardiac, lymphoid, and bone development. The SoxC gene family is represented by Sox4, Sox11, and Sox12. Loss of either Sox4 or Sox11 function is lethal during mouse embryogenesis. Here, we demonstrate that sox4 and sox11 are strongly expressed in the developing eye, heart as well as brain in Xenopus laevis. Morpholino oligonucleotide mediated knock-down approaches in anterior neural tissue revealed that interference with either Sox4 or Sox11 function affects eye development. A detailed analysis demonstrated strong effects on eye size and retinal lamination. Neural induction was unaffected upon Sox4 or Sox11 MO injection and early eye field differentiation and cell proliferation were only mildly affected. Depletion of both genes, however, led independently to a significant increase in cell apoptosis in the eye. In summary, Sox4 and Sox11 are required for Xenopus visual system development.


Asunto(s)
Ojo/embriología , Regulación del Desarrollo de la Expresión Génica/fisiología , Factores de Transcripción SOXC/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriología , Animales , Apoptosis/genética , Encéfalo/metabolismo , Proliferación Celular , Clonación Molecular , Ojo/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Hibridación in Situ , Etiquetado Corte-Fin in Situ , Morfolinos/genética , Miocardio/metabolismo , Estadísticas no Paramétricas
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