Dynamic patterning by morphogens illuminated by cis-regulatory studies

Abstract

Morphogen concentration changes in space as well as over time during development. However, how these dynamics are interpreted by cells to specify fate is not well understood. Here, we focus on two morphogens: the maternal transcription factors Bicoid and Dorsal, which directly regulate target genes to pattern Drosophila embryos. The actions of these factors at enhancers has been thoroughly dissected and provides a rich platform for understanding direct input by morphogens and their changing roles over time. Importantly, Bicoid and Dorsal do not work alone; we also discuss additional inputs that work with morphogens to control spatiotemporal gene expression in embryos.

Chromatin accessibility is a two-tier process regulated by transcription factor pioneering and enhancer activation

“…As another way of internally validating the importance of these motifs, we performed in silico mutagenesis (Figure 2d; Supplemental figure 8). As expected, mutating a Zelda motif in the sog shadow enhancer strongly reduced the predicted chromatin accessibility for all time points, but mutating a Dorsal motif also weakly reduced the predicted accessibility, especially at the later time points when patterning TFs bind most strongly 5,78 . Taken together, the interpretations agree with the TF binding model and our understanding of patterning TF binding dynamics in the Drosophila embryo, suggesting that it is a useful model to probe the rules of chromatin accessibility.…”

“…The first embryo collection (1-1.5 h after egg laying, AEL) covers the time when Zelda begins to bind throughout the genome in the 8th nuclear cycle 36 , as well as the earliest stages of embryonic patterning. During the second collection (1.5-2 h AEL), patterning TFs become active and the major burst of zygotic transcription begins and continues into the third (2-2.5 h AEL) and fourth (2.5-3 h AEL) collections 34,78 . All experiments were performed in triplicate, with highly correlated replicates (Supplemental figure 5).…”

BMP Signaling: Lighting up the Way for Embryonic Dorsoventral Patterning

“…The maternal factors activate zygotic activation of BMP ( Schier and Talbot, 2001 ; Shieh et al, 2014 ; Kobayashi et al, 2018 ; Zhang et al, 2020 ). Activation of bozozok on the dorsal organizer ( Goutel et al, 2000 ; Schier and Talbot, 2001 ; Leung et al, 2003 ; Sidi et al, 2003 ; Ro and Dawid, 2009 ; Irizarry and Stathopoulos, 2021 ) Activation of BMP inhibitors on the dorsal organizer ( Cha et al, 2008 ; Hikasa and Sokol, 2013 ; Bier and De Robertis, 2015 ; Ding et al, 2017 ).…”

“…Moreover, bmp2b expression has expanded to the dorsal margin and dorsal yolk syncytial layer in zebrafish bozozok mutants ( Koos and Ho, 1999 ). In addition, the stability of the Bozozok protein is tightly controlled by the ubiquitin E3 ligase Lnx-2b ( Ro and Dawid, 2009 ; Irizarry and Stathopoulos, 2021 ). The B1 SOX transcription factors have also been reported to regulate DV establishment by controlling bmp2b/7 expression ( Okuda et al, 2010 ; Ranawakage et al, 2020 ).…”

“…For instance, in Drosophila , the DV axis is mainly formed by reciprocal interaction between maternal and zygotic genes. The maternal gene dorsal is ubiquitously expressed in the oocyte, as is the Dorsal protein ( Zeitlinger et al, 2007 ; Irizarry and Stathopoulos, 2021 ). Cactus, the fly orthologue of the mammalian transcription factor NFκB, inhibits Dorsal ( Stevens et al, 2021 ).…”