RESUMEN
Most animals display retarded growth in adverse conditions; however, upon the removal of unfavorable factors, they often show quick growth restoration, which is known as "catch-up" growth. In zebrafish embryos, hypoxia causes growth arrest, but subsequent reoxygenation induces catch-up growth. Here, we report the role of insulin receptor substrate (Irs)1-mediated insulin/insulinlike growth factor signaling (IIS) and the involvement of stem cells in catch-up growth in reoxygenated zebrafish embryos. Disturbed irs1 expression attenuated IIS, resulting in greater inhibition in catch-up growth than in normal growth and forced IIS activationârestored catch-up growth. The irs1 knockdown induced noticeable cell death in neural crest cells (NCCs; multipotent stem cells) under hypoxia, and the pharmacological/genetic ablation of NCCs hindered catch-up growth. Furthermore, inhibition of the apoptotic pathway by pan-caspase inhibition or forced activation of Akt signaling in irs1 knocked-down embryos blocked NCC cell death and rescued catch-up growth. Our data indicate that this multipotent stem cell is indispensable for embryonic catch-up growth and that Irs1-mediated IIS is a prerequisite for its survival under severe adverse environments such as prolonged hypoxia.
Asunto(s)
Embrión no Mamífero/metabolismo , Desarrollo Embrionario/fisiología , Proteínas Sustrato del Receptor de Insulina/metabolismo , Células Madre Multipotentes/metabolismo , Cresta Neural/metabolismo , Transducción de Señal/fisiología , Animales , Hipoxia/metabolismo , Proteínas Sustrato del Receptor de Insulina/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pez CebraRESUMEN
BACKGROUND: Congenital loss of the SHOX gene is considered to be a genetic cause of short stature phenotype in Turner syndrome and Leri-Weill dyschondrosteosis patients. Though SHOX expression initiates during early fetal development, little is known about the embryonic roles of SHOX. The evolutionary conservation of the zebrafish shox gene and the convenience of the early developmental stages for analyses make zebrafish a preferred model. Here, we characterized structure, expression, and developmental roles of zebrafish shox through a loss-of-function approach. RESULTS: We found a previously undiscovered Shox protein that has both a homeodomain and an OAR-domain in zebrafish. The shox transcript emerged during the segmentation period and it increased in later stages. The predominant domains of shox expression were mandibular arch, pectoral fin, anterior notochord, rhombencephalon, and mesencephalon, suggesting that Shox is involved in bone and neural development. Translational blockade of Shox mRNA by an antisense morpholino oligo delayed embryonic growth, which was restored by the co-overexpression of morpholino-resistant Shox mRNA. At later stages, impaired Shox expression markedly delayed the calcification process in the anterior vertebral column and craniofacial bones. CONCLUSIONS: Our data demonstrate evolutionarily conserved Shox plays roles in early embryonic growth and in later bone formation.
Asunto(s)
Embrión no Mamífero/embriología , Proteínas de Homeodominio/metabolismo , Osteogénesis/fisiología , Proteínas de Pez Cebra/metabolismo , Pez Cebra/embriología , Animales , Embrión no Mamífero/citología , Huesos Faciales/citología , Huesos Faciales/embriología , Proteínas de Homeodominio/genética , Columna Vertebral/citología , Columna Vertebral/embriología , Pez Cebra/genética , Proteínas de Pez Cebra/genéticaRESUMEN
The Cancer Control Act has come into effect in 2007. As an important idea of the act, a regional based hospital for cancer treatment and care should respect cancer patient's autonomy and improve his/her quality of life. We have organized PINK (Palliative Care Interactive Network in Kawagoe)in order to fulfill the idea in practical palliative care. Our activities are: Annual conference, Civic forum on Relay for Life in Kawagoe , Patients' association, and Case study examination using our mailing list. This network was built based on our activities to realize an important idea of the Cancer Control Act.