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Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila.

ABSTRACT: Cooperative interactions by DNA-binding proteins have been implicated in cell-fate decisions in a variety of organisms. To date, however, there are few examples in which the importance of such interactions has been explicitly tested in vivo. Here, we tested the importance of cooperative DNA binding by the Bicoid protein in establishing a pattern along the anterior-posterior axis of the early Drosophila embryo. We found that bicoid mutants specifically defective in cooperative DNA binding fail to direct proper development of the head and thorax, leading to embryonic lethality. The mutants did not faithfully stimulate transcription of downstream target genes such as hunchback (hb), giant, and Krüppel. Quantitative analysis of gene expression in vivo indicated that bcd cooperativity mutants were unable to accurately direct the extent to which hb is expressed along the anterior-posterior axis and displayed a reduced ability to generate sharp on/off transitions for hb gene expression. These failures in precise transcriptional control demonstrate the importance of cooperative DNA binding for embryonic patterning in vivo.

SUBMITTER: Lebrecht D

PROVIDER: S-EPMC1201621 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature

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Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila.

Lebrecht Danielle D Foehr Marisa M Smith Eric E Lopes Francisco J P FJ Vanario-Alonso Carlos E CE Reinitz John J Burz David S DS Hanes Steven D SD

Proceedings of the National Academy of Sciences of the United States of America 20050906 37

Cooperative interactions by DNA-binding proteins have been implicated in cell-fate decisions in a variety of organisms. To date, however, there are few examples in which the importance of such interactions has been explicitly tested in vivo. Here, we tested the importance of cooperative DNA binding by the Bicoid protein in establishing a pattern along the anterior-posterior axis of the early Drosophila embryo. We found that bicoid mutants specifically defective in cooperative DNA binding fail to ...[more]

PMID: 16150708

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Project description:BACKGROUND:During development, embryos decode maternal morphogen inputs into highly precise zygotic gene expression. The discovery of the morphogen Bicoid and its profound effect on developmental programming in the Drosophila embryo has been a cornerstone in understanding the decoding of maternal inputs. Bicoid has been described as a classical morphogen that forms a concentration gradient along the antero-posterior axis of the embryo by diffusion and initiates expression of target genes in a concentration-dependent manner in the syncytial blastoderm. Recent work has emphasized the stability of the Bicoid gradient as a function of egg length and the role of nuclear dynamics in maintaining the Bicoid gradient. Bicoid and nuclear dynamics were observed but not modulated under the ideal conditions used previously. Therefore, it has not been tested explicitly whether a temporally stable Bicoid gradient prior to cellularization is required for precise patterning. PRINCIPAL FINDINGS:Here, we modulate both nuclear dynamics and the Bicoid gradient using laminar flows of different temperature in a microfluidic device to determine if stability of the Bicoid gradient prior to cellularization is essential for precise patterning. Dramatic motion of both cytoplasm and nuclei was observed prior to cellularization, and the Bicoid gradient was disrupted by nuclear motion and was highly abnormal as a function of egg length. Despite an abnormal Bicoid gradient during cycles 11-13, Even-skipped patterning in these embryos remained precise. CONCLUSIONS:These results indicate that the stability of the Bicoid gradient as a function of egg length is nonessential during syncytial blastoderm stages. Further, presumably no gradient formed by simple diffusion on the scale of egg length could be responsible for the robust antero-posterior patterning observed, as severe cytoplasmic and nuclear motion would disrupt such a gradient. Additional mechanisms for how the embryo could sense its dimensions and interpret the Bicoid gradient are discussed.

Project description:Transformation from the bilaterally symmetric embryonic aortic arches to the mature great vessels is a complex morphogenetic process, requiring both vasculogenic and angiogenic mechanisms. Early aortic arch development occurs simultaneously with rapid changes in pulsatile blood flow, ventricular function, and downstream impedance in both invertebrate and vertebrate species. These dynamic biomechanical environmental landscapes provide critical epigenetic cues for vascular growth and remodeling. In our previous work, we examined hemodynamic loading and aortic arch growth in the chick embryo at Hamburger-Hamilton stages 18 and 24. We provided the first quantitative correlation between wall shear stress (WSS) and aortic arch diameter in the developing embryo, and observed that these two stages contained different aortic arch patterns with no inter-embryo variation. In the present study, we investigate these biomechanical events in the intermediate stage 21 to determine insights into this critical transition. We performed fluorescent dye microinjections to identify aortic arch patterns and measured diameters using both injection recordings and high-resolution optical coherence tomography. Flow and WSS were quantified with 3D computational fluid dynamics (CFD). Dye injections revealed that the transition in aortic arch pattern is not a uniform process and multiple configurations were documented at stage 21. CFD analysis showed that WSS is substantially elevated compared to both the previous (stage 18) and subsequent (stage 24) developmental time-points. These results demonstrate that acute increases in WSS are followed by a period of vascular remodeling to restore normative hemodynamic loading. Fluctuations in blood flow are one possible mechanism that impacts the timing of events such as aortic arch regression and generation, leading to the variable configurations at stage 21. Aortic arch variations noted during normal rapid vascular remodeling at stage 21 identify a temporal window of increased vulnerability to aberrant aortic arch morphogenesis with the potential for profound effects on subsequent cardiovascular morphogenesis.

Dataset Information

Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila.

Publications

Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila.

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