Multiple roles of mouse Numb in tuning developmental cell fates.

Details

Serval ID
serval:BIB_99E9DA45DEBB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multiple roles of mouse Numb in tuning developmental cell fates.
Journal
Current biology
Author(s)
Zilian O., Saner C., Hagedorn L., Lee H.Y., Säuberli E., Suter U., Sommer L., Aguet M.
ISSN
0960-9822
Publication state
Published
Issued date
2001
Peer-reviewed
Oui
Volume
11
Number
7
Pages
494-501
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
BACKGROUND: Notch signaling regulates multiple differentiation processes and cell fate decisions during both invertebrate and vertebrate development. Numb encodes an intracellular protein that was shown in Drosophila to antagonize Notch signaling at binary cell fate decisions of certain cell lineages. Although overexpression experiments suggested that Numb might also antagonize some Notch activity in vertebrates, the developmental processes in which Numb is involved remained elusive. RESULTS: We generated mice with a homozygous inactivation of Numb. These mice died before embryonic day E11.5, probably because of defects in angiogenic remodeling and placental dysfunction. Mutant embryos had an open anterior neural tube and impaired neuronal differentiation within the developing cranial central nervous system (CNS). In the developing spinal cord, the number of differentiated motoneurons was reduced. Within the peripheral nervous system (PNS), ganglia of cranial sensory neurons were formed. Trunk neural crest cells migrated and differentiated into sympathetic neurons. In contrast, a selective differentiation anomaly was observed in dorsal root ganglia, where neural crest--derived progenitor cells had migrated normally to form ganglionic structures, but failed to differentiate into sensory neurons. CONCLUSIONS: Mouse Numb is involved in multiple developmental processes and required for cell fate tuning in a variety of lineages. In the nervous system, Numb is required for the generation of a large subset of neuronal lineages. The restricted requirement of Numb during neural development in the mouse suggests that in some neuronal lineages, Notch signaling may be regulated independently of Numb.
Keywords
Animals, Body Patterning, Cell Differentiation, Cell Division, Cell Lineage, Central Nervous System, Embryo, Mammalian, Embryonic and Fetal Development, Gene Targeting, Membrane Proteins, Mice, Nerve Tissue Proteins, Neural Tube Defects, Neurons, Receptors, Notch, Recombination, Genetic, Sequence Deletion, Signal Transduction, Spinal Cord, Stem Cells
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:36
Last modification date
20/08/2019 15:01
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