Expression of the Notch 3 intracellular domain in mouse central nervous system progenitor cells is lethal and leads to disturbed neural tube development
نویسندگان
چکیده
Notch-like receptors are found in organisms ranging from nematodes to mammals. In Drosophila, Notch plays a key role in cell fate decisions in the early nervous system. In this report we analyse the effects of excess Notch 3 activity in central nervous system (CNS) progenitor cells. A mutated Notch gene encoding the intracellular domain of mouse Notch 3 transcribed from the nestin promoter was expressed in CNS progenitor cells in transgenic mice. This mutation resulted in a phenotypic series of neural tube defects in embryonic day 10.5-12.5 embryos and proved lethal to embryos beyond this age. In the milder phenotype the neural tube displayed a zig-zag morphology and the CNS was slightly enlarged. More severely affected embryos showed a lack of closure of the anterior neural pore, resulting in the externalization of neural tissue and the complete collapse of the third and fourth ventricles. The expanded ventricular zone of the neuroepithelium, a correspondingly enlarged area of nestin expression, and an increase in the number of proliferating cells in the neural tube suggested that these phenotypes resulted from an expanded CNS progenitor cell population. These data provide support in vivo for the notion that Notch activity plays a role in mammalian CNS development and may be required to guide CNS progenitor cells in their choice between continued proliferation or neuronal differentiation.
منابع مشابه
P50: Selective HCRTR2 Antagonism Increases Embryonic Mouse Cortex Neural Stem Progenitor Cells Proliferation
In multiple sclerosis Oligodendrocytes are obliterated by the immune system. neural stem/ progenitor cells (NS/P Cs) have the capacity to differentiate into mature myelinating oligodendrocytes. In embryonic mouse cortex oligodendrocyte progenitor cells (OPCs) are more abundant than the ganglionic eminence. Doing gene set enrichment analysis using DAVID and Panther websites it was shown that Gpr...
متن کاملEffect of arsenic on neural tube in mouse embryo and relation to reduced folate carrier (RFC-1)
Arsenic is an important environmental toxicant which is usually found in drinking water in inorganic form. The hypothesis tested in this investigation is; arsenic exposure causes neural tube defects (NTDs) andthese defects of the central nervous system are more likely related to folate deficiency during fetal life. In this study, sodium arsenate was administered via intraperitoneal route at a r...
متن کاملFingolimod Enhances Oligodendrocyte Differentiation of Transplanted Human Induced Pluripotent Stem Cell-Derived Neural Progenitors
Multiple sclerosis (MS) is an autoimmune disease which affects myelin in the central nervous system (CNS) and leads to serious disability. Currently available treatments for MS mainly suppress the immune system. Regenerative medicine-based approaches attempt to increase myelin repair by targeting endogenous progenitors or transplanting stem cells or their derivatives. Fingolimod exerts anti-inf...
متن کاملFingolimod Enhances Oligodendrocyte Differentiation of Transplanted Human Induced Pluripotent Stem Cell-Derived Neural Progenitors
Multiple sclerosis (MS) is an autoimmune disease which affects myelin in the central nervous system (CNS) and leads to serious disability. Currently available treatments for MS mainly suppress the immune system. Regenerative medicine-based approaches attempt to increase myelin repair by targeting endogenous progenitors or transplanting stem cells or their derivatives. Fingolimod exerts anti-inf...
متن کاملComplementary and combinatorial patterns of Notch gene family expression during early mouse development
The Drosophila Notch gene encodes a transmembrane receptor involved in the regulation of cell fate. It exerts its effect by lateral specification, inductive signaling and is also important for cell adhesion and axonal pathfinding. In this report we analyse the expression of the three mammalian Notch homologues during early mouse development by in situ hybridization. The Notch 1, 2 and 3 genes s...
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:
- Mechanisms of Development
دوره 59 شماره
صفحات -
تاریخ انتشار 1996