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The Mouse Hindbrain As a Model for Studying Embryonic Neurogenesis
Published on: January 29, 2018
Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development
B W Howell1, T M Herrick, J D Hildebrand
1Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. HowellB@ninds.nih.gov
Current Biology : CB
|August 26, 2000
Summary
Reelin (Reln) signaling requires Dab1 tyrosine phosphorylation, not its downregulation, for proper neuronal migration. Mutating Dab1 phosphorylation sites causes a phenotype similar to Reln deficiency.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- The extracellular protein Reelin (Reln) is crucial for neuronal migration in the brain.
- Absence of Reln leads to increased Dab1 protein and decreased Dab1 tyrosine phosphorylation.
- Loss of Reln receptors (ApoER2, VLDLR) mimics the Reln-deficient phenotype with increased Dab1.
Purpose of the Study:
- To investigate if Dab1 tyrosine phosphorylation influences its protein expression and embryonic neuron positioning.
- To determine the role of Dab1 tyrosine phosphorylation in Reelin signaling.
Main Methods:
- Identified Dab1 tyrosine phosphorylation sites.
- Generated mice with mutated Dab1 tyrosine phosphorylation sites.
- Analyzed the phenotype of mice expressing non-phosphorylated Dab1.
Main Results:
- Mutant Dab1 lacking tyrosine phosphorylation sites was not upregulated like wild-type Dab1 in Reln or receptor mutants.
- Mice expressing non-phosphorylated Dab1 exhibited a phenotype similar to mice lacking Dab1 entirely.
- Dab1 protein is downregulated by Reln signaling only when tyrosine phosphorylation is absent.
Conclusions:
- Dab1 tyrosine phosphorylation sites are essential for Reelin signaling.
- Dab1 downregulation, not its phosphorylation status, is not the primary mechanism for Reelin signaling.
