Plag1 and Plagl2 have overlapping and distinct functions in telencephalic development

Author:

Adnani Lata12,Dixit Rajiv12,Chen Xingyu2,Balakrishnan Anjali13,Modi Harshil1,Touahri Yacine1,Logan Cairine4,Schuurmans Carol123ORCID

Affiliation:

1. Sunnybrook Research Institute, Biological Sciences Platform, Room S1-16, 2075 Bayview Ave, Toronto, ON, Canada

2. Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N 4N1, Canada

3. Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada

4. Department of Cell Biology and Anatomy, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada

Abstract

The Plag gene family has three members; Plagl1/Zac1, which is a tumour suppressor gene, and Plag1 and Plagl2, which are proto-oncogenes. All three genes are known to be expressed in embryonic neural progenitors, and Zac1 regulates proliferation, neuronal differentiation and migration in the developing neocortex. Here we examined the functions of Plag1 and Plagl2 in neocortical development. We first attempted, and were unable to generate, E12.5 Plag1;Plagl2 double mutants, indicating that at least one Plag1 or Plagl2 gene copy is required for embryonic survival. We therefore focused on single mutants, revealing a telencephalic patterning defect in E12.5 Plagl2 mutants and a proliferation/differentiation defect in Plag1 mutant neocortices. Specifically, the ventral pallium, a dorsal telencephalic territory, expands into the ventral telencephalon in Plagl2 mutants. In contrast, Plag1 mutants develop normal regional territories, but neocortical progenitors proliferate less and instead produce more neurons. Finally, in gain-of-function studies, both Plag1 and Plagl2 reduce neurogenesis and increase BrdU-uptake, indicative of enhanced proliferation, but while Plagl2 effects on proliferation are more immediate, Plag1 effects are delayed. Taken together, we found that the Plag proto-oncogenes genes are essential regulators of neocortical development and although Plag1 and Plagl2 functions are similar, they do not entirely overlap.

Funder

March of Dimes Canada

Canadian Institutes of Health Research

Natural Sciences and Engineering Research Council of Canada

Alberta Children's Hospital Research Institute

Alberta Innovates - Health Solutions

University of Calgary

Publisher

The Company of Biologists

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology

Reference104 articles.

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