RESUMEN
In many invertebrates, the nuclearization of ß-catenin at one pole of the embryo initiates endomesoderm specification. An intriguing possibility is that a gradient of nuclear ß-catenin (nß-catenin), similar to that operating in vertebrate neural tube patterning, functions to distinguish cell fates in invertebrates. To test this hypothesis, we determined the function of nß-catenin during the early development of the sea star, which undergoes a basal deuterostomal mode of embryogenesis. We show that low levels of nß-catenin activity initiate bra, which is expressed in the future posterior endoderm-fated territory; intermediate levels are required for expression of foxa and gata4/5/6, which are later restricted to the endoderm; and activation of ets1 and erg in the mesoderm-fated territory requires the highest nß-catenin activity. Transcription factors acting downstream of high nß-catenin segregate the endoderm/mesoderm boundary, which is further reinforced by Delta/Notch signaling. Significantly, therefore, in sea stars, endomesoderm segregation arises through transcriptional responses to levels of nß-catenin activity. Here, we describe the first empirical evidence of a dose-dependent response to a dynamic spatiotemporal nß-catenin activity that patterns cell fates along the primary axis in an invertebrate.
Asunto(s)
Tipificación del Cuerpo , Núcleo Celular/metabolismo , Endodermo/embriología , Mesodermo/embriología , beta Catenina/metabolismo , Animales , Blástula/efectos de los fármacos , Blástula/metabolismo , Tipificación del Cuerpo/efectos de los fármacos , Tipificación del Cuerpo/genética , Núcleo Celular/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/metabolismo , Endodermo/efectos de los fármacos , Endodermo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Redes Reguladoras de Genes , Factor Nuclear 3-gamma del Hepatocito/metabolismo , Cloruro de Litio/farmacología , Mesodermo/efectos de los fármacos , Mesodermo/metabolismo , Modelos Biológicos , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Estrellas de Mar/embriología , Estrellas de Mar/genética , Factores de Tiempo , Transcripción Genética/efectos de los fármacosRESUMEN
We identified a 41.4% prevalence of hepatitis C virus, absence of HIV, and unexpectedly high frequency of hepatitis C virus genotype 3 among suburban New Jersey heroin users 17-35 years of age during 2014-2015. Despite 2 clinicians prepared to engage these users, few were successfully linked to care and treated.
Asunto(s)
Consumidores de Drogas , Hepacivirus , Hepatitis C/epidemiología , Hepatitis C/transmisión , Heroína , Población Suburbana , Adolescente , Adulto , Hepatitis C/virología , Heroína/administración & dosificación , Humanos , Incidencia , New Jersey/epidemiología , Prevalencia , Adulto JovenRESUMEN
The Wnt signaling pathway is highly conserved across metazoa and has pleiotropic functions in the development of many animals. Binding of a secreted Wnt ligand to its Frizzled (Fz) receptor activates Dishevelled, which then drives one of three major signaling cascades, canonical (ß-catenin), calcium, or planar cell polarity signaling. These pathways have distinct developmental effects and function in different processes in different organisms. Here we report the expression of six wnt and three fz genes during embryogenesis of the sea star, Patiria miniata, as a first step in uncovering the roles of Wnt signaling in the development of this organism. wnt3, wnt4, wnt8, and wnt16 are expressed in nested domains in the endoderm and lateral ectoderm from blastula through late gastrula stages; wnt2 and wnt5 are expressed in the mesoderm and anterior endoderm. Expression of different fz paralogs is detected in the mesoderm; posterior endoderm and ectoderm; and anterior ectoderm. Taken together, this suggests that Wnt signaling can occur throughout most of the embryo and may therefore play multiple roles during sea star development.