Uncovering a Dynamic Feature of the Transcriptional Regulatory Network for Anterior-Posterior Patterning in the Drosophila Embryo

Abstract

Anterior-posterior (AP) patterning in the Drosophila embryo is dependent on the Bicoid (Bcd) morphogen gradient. However, most target genes of Bcd also require additional inputs to establish their expression domains, reflective of the operation of a cross-regulatory network and contributions of other maternal signals. This is in contrast to hunchback (hb), which has an anterior expression domain driven by an enhancer that appears to respond primarily to the Bcd input. To gain a better understanding of the regulatory logic of the AP patterning network, we perform quantitative studies that specifically investigate the dynamics of hb transcription during development. We show that Bcd-dependent hb transcription, monitored by the intron-containing nascent transcripts near the P2 promoter, is turned off quickly–on the order of a few minutes–upon entering the interphase of nuclear cycle 14A. This shutdown contrasts with earlier cycles during which active hb transcription can persist until the moment when the nucleus enters mitosis. The shutdown takes place at a time when the nuclear Bcd gradient profile in the embryo remains largely intact, suggesting that this is a process likely subject to control of a currently unknown regulatory mechanism. We suggest that this dynamic feature offers a window of opportunity for hb to faithfully interpret, and directly benefit from, Bcd gradient properties, including its scaling properties, to help craft a robust AP patterning outcome.

Adaptation of the length scale and amplitude of the Bicoid gradient profile to achieve robust patterning in abnormally large Drosophila melanogaster embryos

“…Bcddependent hb transcription is a highly dynamic process and it becomes turned off quickly (in the order of just a few minutes) after the embryo enters the interphase of nuclear cycle 14 (Liu and Ma, 2013a;Liu and Ma, 2013b). It has been proposed that this dynamic property represents a mechanism that enables the embryo to benefit directly and faithfully from the scaling properties of the Bcd gradient through the formation of a scaled hb boundary near mid embryo (Liu and Ma, 2013a). Our analysis of the eve expression pattern (Fig.…”

“…The hb boundary is a montage (Liu and Ma, 2013a) of two overlapping boundaries that have distinct temporal dynamics and respond to distinct regulatory inputs. But our recent studies show that perturbations of Bcd gradient properties can directly lead to corresponding changes in hb expression (He et al, 2008;He et al, 2010a;He et al, 2010b;He et al, 2011;He et al, 2012), suggesting that the positioning of the hb boundary is determined primarily by the Bcd gradient input.…”

“…But our recent studies show that perturbations of Bcd gradient properties can directly lead to corresponding changes in hb expression (He et al, 2008;He et al, 2010a;He et al, 2010b;He et al, 2011;He et al, 2012), suggesting that the positioning of the hb boundary is determined primarily by the Bcd gradient input. Bcddependent hb transcription is a highly dynamic process and it becomes turned off quickly (in the order of just a few minutes) after the embryo enters the interphase of nuclear cycle 14 (Liu and Ma, 2013a;Liu and Ma, 2013b). It has been proposed that this dynamic property represents a mechanism that enables the embryo to benefit directly and faithfully from the scaling properties of the Bcd gradient through the formation of a scaled hb boundary near mid embryo (Liu and Ma, 2013a).…”

“…A similar approach was used to capture the fluorescence intensities used to establish hb mRNA FISH profiles. In this case, a sliding circle along the dorsal side of the embryo within the cytoplasmic layer was used Liu and Ma, 2013a). Each hb FISH intensity profile was normalized to the average peak values found in the anterior (x/L<0.4) of an embryo.…”

Modulation of temporal dynamics of gene transcription by activator potency in theDrosophilaembryo

“…In Drosophila, a set of cellular events, such as cell cycle lengthening and cellularization, marks a specific stage within this period and is referred to as the mid-blastula transition (MBT) (Tadros and Lipshitz, 2009;Langley et al, 2014;Gebelein and Ma, 2015). During this time there is a massive wave of zygotic gene activation (Pritchard and Schubiger, 1996;De Renzis et al, 2007), which coincides with the receding of an earlier wave of transcription of zygotic genes, such as nullo, Serendipity-α (Sry-α), Sex-lethal (Sxl) and hunchback (hb) (Rose and Wieschaus, 1992;ten Bosch et al, 2006;Erickson and Quintero, 2007;Liu and Ma, 2013b). The mitotic phase is known to be disruptive to transcription prior to nuclear cycle (nc) 14 (Shermoen and O'Farrell, 1991).…”