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Dixdc1 Is a Critical Regulator of DISC1 and Embryonic Cortical Development
Karun K. Singh, Xuecai Ge, Yingwei Mao, Laurel Drane, Konstantinos Meletis, Benjamin A. Samuels, Li-Huei Tsai. The psychiatric illness risk gene Disrupted in Schizophrenia-1 (DISC1) plays an important role in brain development; however, it is unclear how DISC1 is regulated during cortical development. Here....
1 comment to Dixdc1 Is a Critical Regulator of DISC1 and Embryonic Cortical Development |
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Copyright © 2012 The Third Reviewer - All Rights Reserved |
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If anyone else here has read this paper, I am confused about the graph at the right of Figure 8A. I don’t understand what the left, middle, and right groups are, and how in some conditions only 10% of GFP+ cells combined are either uni-, bi-, or multipolar. What other options are there?!
Other than this, and the general lack of detail in some of the figure legends and methods (an all too common problem these days), I think this is a pretty interesting and convincing paper. It’s very interesting to me that there appears to be a migration defect with DISC1 knockdown at later stages, i.e. E15, but not earlier, E13-E14, both here and in the earlier paper, Mao et al., 2009. Compare for example Figure 4A, where if anything DISC1 RNAi at E13 leads to an INCREASE in cells in the cortical plate 3 days later, with Figure 5E, where DISC1 RNAi at E15 completely lacks cells in the CP 4 days later. In contrast, Dixdc1 RNAi impedes radial migration at both early and later time-points. One possible explanation that the authors don’t explicitly consider is that Dixdc1 has two discrete functions related to migration, one of which is potentially completely independent of DISC1. This is suggested by their data in Figure 7B showing that overexpression of Dixdc1 fragment 1 (the N-terminal part with the CH domain) has an equally deleterious effect on radial migration as does fragment 2, which is the DISC1/Ndel1-binding fragment, and which they show inhibits endogenous Dixdc1-DISC1/Ndel1 interaction (Supp Fig 7). Although this is very interesting, it casts doubt on the model that a Dixdc1-DISC1 interaction is at all involved in regulating migration; rather the data seem to be consistent with each protein being involved independently in radial migration. (In that light, also interesting to note that the phospho-mutant Dixdc1 Ser250Ala did not show impaired binding to DISC1.)
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