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Plag1 and Plagl2 have overlapping and distinct functions in telencephalic development
Lata Adnani1,2, Rajiv Dixit1,2, Xingyu Chen2
1Sunnybrook Research Institute, Biological Sciences, Room S1-16A, 2075 Bayview Ave, Toronto, ON, Canada M4N 3M5.
Biology Open
|October 27, 2018
Summary
The Plag gene family, including Plag1 and Plagl2 proto-oncogenes, is crucial for neocortical development. These genes regulate neural progenitor proliferation and differentiation, impacting embryonic survival and brain patterning.
Area of Science:
- Developmental Neuroscience
- Molecular Biology
- Genetics
Background:
- The Plag gene family comprises tumor suppressor (Plagl1/Zac1) and proto-oncogene (Plag1, Plagl2) members.
- These genes are expressed in embryonic neural progenitors, with Zac1 known to regulate neocortical development.
Purpose of the Study:
- To investigate the functions of Plag1 and Plagl2 in mammalian neocortical development.
- To determine the roles of Plag1 and Plagl2 in neural progenitor proliferation, differentiation, and telencephalic patterning.
Main Methods:
- Generation and analysis of Plag1 and Plagl2 single and double knockout mouse models.
- Examination of embryonic day E12.5 embryos for developmental defects.
- Gain-of-function studies to assess the impact of Plag1 and Plagl2 expression on neurogenesis and proliferation (BrdU uptake).
Main Results:
- Plag1 and Plagl2 are essential for embryonic survival, as double mutants could not be generated.
- Plagl2 mutants exhibit telencephalic patterning defects, with ventral pallium expansion.
- Plag1 mutants show reduced neocortical progenitor proliferation and increased neuronal differentiation.
- Gain-of-function studies indicate both Plag1 and Plagl2 reduce neurogenesis and enhance proliferation, with distinct temporal effects.
Conclusions:
- Plag1 and Plagl2 proto-oncogenes are essential regulators of neocortical development.
- While sharing similar functions, Plag1 and Plagl2 exhibit non-overlapping roles in regulating neural progenitor behavior and brain patterning.
- These findings highlight the complex roles of the Plag gene family in establishing proper brain architecture.
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