Three-dimensional morphology and gene expression in the Drosophila blastoderm at cellular resolution II: dynamics

BackgroundTo accurately describe gene expression and computationally model animal transcriptional networks, it is essential to determine the changing locations of cells in developing embryos.ResultsUsing automated image analysis methods, we provide the first quantitative description of temporal changes in morphology and gene expression at cellular resolution in whole embryos, using the Drosophila blastoderm as a model. Analyses based on both fixed and live embryos reveal complex, previously undetected three-dimensional changes in nuclear density patterns caused by nuclear movements prior to gastrulation. Gene expression patterns move, in part, with these changes in morphology, but additional spatial shifts in expression patterns are also seen, supporting a previously proposed model of pattern dynamics based on the induction and inhibition of gene expression. We show that mutations that disrupt either the anterior/posterior (a/p) or the dorsal/ventral (d/v) transcriptional cascades alter morphology and gene expression along both the a/p and d/v axes in a way suggesting that these two patterning systems interact via both transcriptional and morphological mechanisms.ConclusionOur work establishes a new strategy for measuring temporal changes in the locations of cells and gene expression patterns that uses fixed cell material and computational modeling. It also provides a coordinate framework for the blastoderm embryo that will allow increasingly accurate spatio-temporal modeling of both the transcriptional control network and morphogenesis.

[1]  D. Poulson,et al.  The embryonic development of drosophila melanogaster , 1937 .

[2]  J. Mohler.  Developmental genetics of the Drosophila egg. I. Identification of 59 sex-linked cistrons with maternal effects on embryonic development. , 1977, Genetics.

[3]  T. W. Ridler,et al.  Picture thresholding using an iterative selection method. , 1978 .

[4]  B. Alberts,et al.  Studies of nuclear and cytoplasmic behaviour during the five mitotic cycles that precede gastrulation in Drosophila embryogenesis. , 1983, Journal of cell science.

[5]  Bernard W. Silverman,et al.  Density Estimation for Statistics and Data Analysis , 1987 .

[6]  K. Anderson.  Dorsal—ventral embryonic pattern genes of Drosophila , 1987 .

[7]  S. Carroll,et al.  Genes that control dorsoventral polarity affect gene expression along the anteroposterior axis of the Drosophila embryo. , 1987, Development.

[8]  P. Ingham.  The molecular genetics of embryonic pattern formation in Drosophila , 1988, Nature.

[9]  P. J. Green,et al.  Density Estimation for Statistics and Data Analysis , 1987 .

[10]  C. Nüsslein-Volhard,et al.  The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner , 1988, Cell.

[11]  A. Mahowald,et al.  Developmental genetics of the gastrulation defective locus in Drosophila melanogaster. , 1988, Developmental biology.

[12]  M. Erdélyi,et al.  Isolation and characterization of dominant female sterile mutations of Drosophila melanogaster. II. Mutations on the second chromosome. , 1989, Genetics.

[13]  M. Erdélyi,et al.  Isolation and characterization of dominant female sterile mutations of Drosophila melanogaster. I. Mutations on the third chromosome. , 1989, Genetics.

[14]  K. Struhl,et al.  The gradient morphogen bicoid is a concentration-dependent transcriptional activator , 1989, Cell.

[15]  B. Alberts,et al.  daughterless-abo-like, a Drosophila maternal-effect mutation that exhibits abnormal centrosome separation during the late blastoderm divisions. , 1990, Development.

[16]  Stuart A. Kauffman,et al.  The origins of order , 1993 .

[17]  K. Anderson,et al.  Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsal-ventral polarity in the Drosophila embryo. , 1991, Genes & development.

[18]  William H. Press,et al.  The Art of Scientific Computing Second Edition , 1998 .

[19]  M Hoch,et al.  Transcriptional control by Drosophila gap genes , 1992, Journal of Cell Science.

[20]  P. Lawrence.  The making of a fly , 1992 .

[21]  H. Jäckle,et al.  Transcriptional regulation and spatial patterning in Drosophila. , 1993, Current opinion in genetics & development.

[22]  Carl-Fredrik Westin,et al.  Normalized Convolution : Technique for Filtering Incomplete and Uncertain Data , 1993 .

[23]  M. Noll,et al.  Complex regulation of early paired expression: initial activation by gap genes and pattern modulation by pair-rule genes. , 1993, Development.

[24]  L. Pick,et al.  Non-periodic cues generate seven ftz stripes in the Drosophila embryo , 1995, Mechanisms of Development.

[25]  C. Hashimoto,et al.  Ventralization of the Drosophila embryo by deletion of extracellular leucine-rich repeats in the Toll protein. , 1995, Molecular biology of the cell.

[26]  Arantxa Etxeverria.  The Origins of Order , 1993 .

[27]  E. Wieschaus,et al.  Integration of the head and trunk segmentation systems controls cephalic furrow formation in Drosophila. , 1997, Development.

[28]  J. Bonner.  Cells, embryos, and evolution: Toward a cellular and developmental understanding of phenotypic variation and evolutionary adaptability , 1998 .

[29]  R. Saint,et al.  A His2AvDGFP fusion gene complements a lethal His2AvD mutant allele and provides an in vivo marker for Drosophila chromosome behavior. , 1999, DNA and cell biology.

[30]  C. Hashimoto,et al.  Gastrulation defective is a serine protease involved in activating the receptor toll to polarize the Drosophila embryo. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R. Delotto,et al.  Interallelic complementation at the Drosophila melanogaster gastrulation defective locus defines discrete functional domains of the protein. , 2001, Genetics.

[32]  E. Wieschaus,et al.  Two new roles for the Drosophila AP patterning system in early morphogenesis. , 2001, Development.

[33]  Mark D. Biggin,et al.  Mapping organism expression levels at cellular resolution in developing Drosophila , 2001, SPIE BiOS.

[34]  Michael Levine,et al.  Whole-Genome Analysis of Dorsal-Ventral Patterning in the Drosophila Embryo , 2002, Cell.

[35]  Denis Thieffry,et al.  Dynamical modelling of pattern formation during embryonic development. , 2003, Current opinion in genetics & development.

[36]  Pierre Soille,et al.  Morphological Image Analysis: Principles and Applications , 2003 .

[37]  David H. Sharp,et al.  Dynamical Analysis of Regulatory Interactions in the Gap Gene System of Drosophila melanogaster , 2004, Genetics.

[38]  David H. Sharp,et al.  Dynamic control of positional information in the early Drosophila embryo , 2004, Nature.

[39]  W. Bialek,et al.  Diffusion and scaling during early embryonic pattern formation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Bernd Hamann,et al.  Visualization for Validation and Improvement of Three-dimensional Segmentation Algorithms , 2005, EuroVis.

[41]  M. Levine,et al.  Genomic regulatory networks and animal development. , 2005, Developmental cell.

[42]  Charless C. Fowlkes,et al.  3d morphology and gene expression in the drosophila blastoderm at cellular resolution , 2006 .

[43]  Jitendra Malik,et al.  Inferring nuclear movements from fixed material , 2006 .

[44]  Leon Glass,et al.  Reverse Engineering the Gap Gene Network of Drosophila melanogaster , 2006, PLoS Comput. Biol..

[45]  Charless C. Fowlkes,et al.  Three-dimensional morphology and gene expression in the Drosophila blastoderm at cellular resolution I: data acquisition pipeline , 2006, Genome Biology.

[46]  Jitendra Malik,et al.  PointCloudXplore: Visual Analysis of 3D Gene Expression Data Using Physical Views and Parallel Coordinates , 2006, EuroVis.