TAZ Represses the Neuronal Commitment of Neural Stem Cells
Round 1
Reviewer 1 Report
I commend the authors for their good work on the transcriptional co-factor TAZ and its influence on Neural Stem Progenitor Cells (NSPC) of the mammalian brain.
Their identification of TAZ and its expression in NSPC declines with aging will contribute towards reputable knowledge in the field.
However, to further characterize some of the mechanisms involved, it would have been important to see experimental work conducted directly on the cell cycle. The authors do not demonstrate this approach. Accordingly, it will be of higher impact if they can demonstrate this strategy? Respectively.
Can the authors conduct such a strategy before the manuscript is accepted?
Author Response
Please see attached document with answer.
Author Response File: Author Response.pdf
Reviewer 2 Report
In the present study, authors investigated the role of TAZ on neuronal differentiation in vivo and in vitro. Authors showed that TAZ knock-down and forced expression in NSPCs promoted and inhibited neuronal differentiation, respectively. In addition, authors showed that forced expression of TAZ in NSPCs displayed down-regulated expression of Sox2 and proneuronal genes, such as ASCL1, NEUROG2, and NEUROD1. In general, this manuscript is well organized and written. I have a few comments as flowing:
- Fig. 1 and Fig. 2: Although some nestin+ NSPCs expressed TAZ during the development, it seems that there are many TAZ+ cells that lacked nestin expression. Do you know which types of cells express TAZ other than NSPCs during the development?
- Fig. 4A and Fig. 7A: It is better to add the data of nestin and DCX expression.
- Sox2 is an essential factor for directing various types of cells to neuronal lineage (Cell Stem Cell. 2012;11:471-476; Cell Stem Cell. 2012;11:100-109; Cell Stem Cell. 2011;8:538-551) as well as acquiring stemness by somatic cells (Cell. 2007;131:861-872). A previous study showed that forced expression of Sox2 promoted neurogenesis as well as up-regulated expressions of neurogenic transcription factors, such as MASH1 (ASCL1) and NEUROG2 (Stem Cells 2015, 33, 1962-74), indicating that expression patterns of Sox2 and these proneuronal genes may be associated under certain conditions. Please discuss this.
Author Response
Please see attached document with answer
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
I think authors significantly improved their original manuscript based on reviewers’ comments.