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Ex Utero Electroporation and Organotypic Slice Cultures of Embryonic Mouse Brains for Live-Imaging of Migrating GABAergic Interneurons
Published on: April 20, 2018
Dab2ip regulates neuronal migration and neurite outgrowth in the developing neocortex
Gum Hwa Lee1, Sun Hong Kim, Ramin Homayouni
1Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
Plos One
|October 12, 2012
Summary
DOC-2/DAB2 interacting protein (Dab2ip) is crucial for mammalian brain development. This study reveals Dab2ip regulates neuronal migration and neurite development in the embryonic mouse neocortex.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- DOC-2/DAB2 interacting protein (Dab2ip) is a Ras GTPase-activating protein (GAP) family member with known tumor suppressor functions.
- Dab2ip is highly expressed in the brain and interacts with Dab1, a key player in the Reelin pathway regulating brain development and function.
Purpose of the Study:
- To investigate the role of Dab2ip in mammalian cortical development.
- To elucidate the molecular mechanisms by which Dab2ip influences neuronal development.
Main Methods:
- Utilized in utero electroporation to knock down or overexpress Dab2ip in embryonic mouse neocortical progenitor cells.
- Performed structure-function experiments and ex-vivo analysis of transfected neurons.
- Examined neuronal migration, morphology, and neurite development.
Main Results:
- Dab2ip down-regulation and overexpression disrupt neuronal migration, particularly affecting late-born cortical neurons.
- Both the PH and GRD domains of Dab2ip are essential for proper neuronal migration.
- Altered Dab2ip levels disrupt the multipolar to bipolar neuronal transition and affect neurite development and microtubule-associated protein expression.
Conclusions:
- Dab2ip plays a critical, previously unrecognized role in mammalian cortical development.
- Dab2ip is necessary for correct neuronal migration, morphology, and neurite outgrowth.
- This study provides initial insights into the molecular mechanisms underlying Dab2ip's function in brain development.
