Journal
MECHANISMS OF DEVELOPMENT
Volume 122, Issue 10, Pages 1106-1117Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mod.2005.06.005
Keywords
death associated protein kinase1; delta-like1; embryonic day 9.5; immunohistochemistry; knockout; mind bomb1; neurogenesis; Notch1 intracellular domain
Categories
Funding
- NICHD NIH HHS [HD10668] Funding Source: Medline
Ask authors/readers for more resources
The Notch-Delta signaling pathway controls many conserved cell determination events. While the Notch end is fairly well characterized, the Delta end remains poorly understood. Mind bomb 1 (MIB1) is one of two E3 ligases known to ubiquitinate Delta. We report here that a targeted mutation of Mib1 in mice results in embryonic lethality by E10.5. Mutants exhibit multiple defects due to their inability to modulate Notch signaling. As histopathology revealed a strong neurogenic phenotype, this study concentrates on characterizing the Mib1 mutant by analyzing Notch pathway components in embryonic neuroepithelium prior to developmental arrest. Premature neurons were observed to undergo apoptosis soon after differentiation. Aberrant neurogenesis is a direct consequence of lowered Hes1 and Hes5 expression resulting from the inability to generate Notch1 intracellular domain (NICD1). We conclude that MIBI activity is required for S3 cleavage of the Notch1 receptor. These results have direct implications for manipulating the differentiation of neuronal stem cells and provide a putative target for the modulation of specific tumors. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available