Top 3 Biorxiv Papers Today in Developmental Biology


1.997 Mikeys
#1. Klf9 is a key feedforward regulator of the transcriptomic response to glucocorticoid receptor activity
Ian Gans, Ellen I Hartig, Shusen Zhu, Andrea R Tilden, Lucie Hutchins, Nathaniel Maki, Joel H Graber, James A Coffman
The zebrafish has recently emerged as a model system for investigating the developmental roles of glucocorticoid signaling and the mechanisms underlying glucocorticoid-induced developmental programming. To assess the role of the Glucocorticoid Receptor (GR) in such programming, we used CRISPR-Cas9 to produce a new frameshift mutation, GR369-, which unlike previously-reported frameshift mutations eliminates all potential in-frame initiation codons upstream of the DNA binding domain. Using RNA-seq to ask how this mutation affects the larval transcriptome under both normal conditions and with chronic cortisol treatment, we find that GR mediates most of the effects of the treatment, and paradoxically, that the transcriptome of cortisol-treated larvae is more like that of larvae lacking a GR than that of larvae with a GR, suggesting that the cortisol-treated larvae develop GR resistance. The one transcriptional regulator that was both underexpressed in GR369- larvae and consistently upregulated in cortisol-treated larvae was klf9. We...
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Sample Sizes : [10]
Authors: 8
Total Words: 8735
Unqiue Words: 2512

1.994 Mikeys
#2. Interdependent regulation of stereotyped and stochastic photoreceptor fates in the fly eye
Adam C. Miller, Elizabeth Urban, Eric L. Lyons, Tory G. Herman, Robert J. Johnston
Diversification of neuronal subtypes often requires stochastic gene regulatory mechanisms. How stochastically expressed transcription factors interact with other regulators in gene networks to specify cell fates is poorly understood. The random mosaic of color-detecting R7 photoreceptor subtypes in Drosophila is controlled by the stochastic on/off expression of the transcription factor Spineless (Ss). In SsON R7s, Ss induces expression of Rhodopsin 4 (Rh4), whereas in SsOFF R7s, the absence of Ss allows expression of Rhodopsin 3 (Rh3). Here, we find that the transcription factor Runt, which is initially expressed in all R7s, activates expression of Spineless in a random subset of R7s. Later, as R7s develop, Ss negatively feeds back onto Runt to prevent repression of Rh4 and ensure proper fate specification. Together, stereotyped and stochastic regulatory inputs are integrated into feedforward and feedback mechanisms to control cell fate.
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Authors: 5
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1.982 Mikeys
#3. Changing the Waddington landscape to control mesendoderm competence
James R Valcourt, Roya Huang, Sharmistha Kundu, Divya Venkatasubramanian, Robert E Kingston, Sharad Ramanathan
As pluripotent human embryonic stem cells progress along the developmental trajectory towards one differentiated fate, they lose competence to adopt other fates. Here, we show that the loss of competence for alternative fates occurs at a specific point along the developmental trajectory and that this point can be moved using genetic perturbations. We first show that competence to adopt mesendoderm-derived fates in response to BMP4 and Activin A signal exposure is lost during ectoderm-directed differentiation. By monitoring each cell's progression along its developmental trajectory, we can prospectively predict that cell's mesendoderm competence. We then exploit this predictive ability using RNA-seq and ATAC-seq to identify and validate candidate transcription factors that can modulate mesendoderm competence. These factors exert their effects by controlling the cell's progression along the developmental trajectory, by tuning its competence to form mesendoderm at any given point along that trajectory, or by altering both of these...
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Authors: 6
Total Words: 0
Unqiue Words: 0

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