Retinoic-acid-mediated HRas stabilization induces neuronal differentiation of neural stem cells during brain development.
نویسندگان
چکیده
Ras signaling is tightly regulated during neural stem cell (NSC) differentiation, and defects in this pathway result in aberrant brain development. However, the mechanism regulating Ras signaling during NSC differentiation was unknown. Here, we show that stabilized HRas specifically induces neuronal differentiation of NSCs. Lentivirus-mediated HRas overexpression and knockdown resulted in stimulation and inhibition, respectively, of NSC differentiation into neuron in the ex vivo embryo. Retinoic acid, an active metabolite of vitamin A, promoted neuronal differentiation of NSCs by stabilizing HRas, and HRas knockdown blocked the retinoic acid effect. Vitamin-A-deficient mice displayed abnormal brain development with reduced HRas levels and a reduced thickness of the postmitotic region containing differentiated neurons. All of these abnormal phenotypes were rescued with the restoration of HRas protein levels achieved upon feeding with a retinoic-acid-supplemented diet. In summary, this study shows that retinoic acid stabilizes HRas protein during neurogenesis, and that this is required for NSC differentiation into neurons and murine brain development.
منابع مشابه
Analysis of Promyelocytic Leukemia in Human Embryonic Carcinoma Stem Cells During Retinoic Acid-Induced Neural Differentiation
Background: Promyelocytic leukemia protein (PML) is a tumor suppressor protein that is involved in myeloid cell differentiation in response to retinoic acid (RA). In addition, RA acts as a natural morphogen in neural development. Objectives: This study aimed to examine PML gene expression in different stages of in vitro neural differentiation of NT2 cells, and to investigate the possible role o...
متن کاملThe effect of Fibroblast Growth Factor-2(FGF-2) and retinoic acid on differentiation of mouse embryonic stem cells into neural cells
Introduction: Embryonic Stem (ES) cells as pluripotent cells derived from the inner cell mass of blastula can differentiate to neural cells in vitro and this property is valuable in studies of neurogenesis and in the generation of donor cells for transplantation. In this regard, the propose of this research, was the study of the role of two important factors in the development of neural syst...
متن کاملInduction of Human Embryonic Stem Cells into neuronal differentiation by increasing cyclic Adenosine Mono Phosphate
Introduction: To evaluate the cAMP -mediated IBMX (3-IsoButyle -1-Methyl Xanthin) and db-cAMP (dibutyryl cAMP) effects on differentiation of human Embryonic Stem Cells (hESCs) into nerve cells were the objectives of this study. Methods: We have used Royan H1 hESC- derived embryoid bodies with four treatment groups: six days treatment with IBMX (5×10 -4M) and db-cAMP (10 -9M) (referred to as...
متن کاملThe Effect of Astrocyte-Conditioned Medium (ACM) and Retinoic Acid on Neural Differentiation of Mouse Embryonic Stem Cells
Purpose: The aim of this research was to study the properties of factors secreted from astrocyte cells in suspension medium in direct differentiation of mouse embryonic stem cells into neural cells. Materials and Methods: Royan B1 mouse embryonic stem (ES) cells were used in this experiment. For differentiation of Es cells into the neural cells, the astrocyte-condition medium (ACM) of mouse fe...
متن کاملA novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation
Gab proteins amplify and integrate signals stimulated by many growth factors. In culture and animals, retinoic acid (RA) induces neuronal differentiation. We show that Gab2 expression is detected in neurons in three models of neuronal differentiation: embryonic carcinoma (EC) stem cells, embryonic stem cells, and primary neural stem cells (NSCs). RA treatment induces apoptosis, countered by bas...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of cell science
دوره 129 15 شماره
صفحات -
تاریخ انتشار 2016