Drosophila embryogenesis 583031 222012629 2008-06-27T03:45:50Z MitraE 3731668 '''''Drosophila''''' has long been a favorite [[model organism|model system]] for [[genetics|genetic]]ists and [[Developmental biology|development]]al biologists studying '''[[embryogenesis]]'''. The small size, short generation time, and large brood size makes it ideal for genetic studies. Transparent embryos facilitate developmental studies. ''[[Drosophila melanogaster]]'' was introduced into the field of genetic experiments by [[Thomas Hunt Morgan]] in [[1909]]. ==Life cycle== ''Drosophila'' display a holometabolous method of development, meaning that they have three distinct stages of their post-embryonic life cycle, each with radically different body plans: larva, pupa and finally, adult. The machinery necessary for the function and smooth transition between these three phases develops during embryogenesis. During [[embryogenesis]], the larval stage fly will develop and will hatch at a stage of its life known as the first larval instar. Cells that will produce adult structures are put aside in [[imaginal disc]]s. During the pupal stage, the larval body breaks down as the imaginal disks grow and produce the adult body. This process is called ''complete [[metamorphosis (biology)|metamorphosis]]''. The mother fly produces [[oocyte]]s that already have anterior-posterior and dorsal-ventral axes defined by maternal activities. Embryogenesis in ''Drosophila'' is unique among model organisms in that cleavage occurs in a [[syncytium]]. About 5,000 nuclei accumulate in the unseparated cytoplasm of the oocyte before they migrate to the surface and are encompassed by plasma membranes to form cells surrounding the yolk sac. Early on, the [[germ line]] segregates from the somatic cells through the formation of pole cells at the posterior end of the embryo. Like other [[triploblastic]] [[metazoa]], [[gastrulation]] leads to the formation of three [[germ layer]]s: the endoderm, mesoderm, and ectoderm. The mesoderm invaginates from the ventral furrow (VF), as do the ectoderm that will give rise to the midgut. The pole cells are internalized by a different route. Germ band elongation involves many rearrangements of cells, and the appearance of distinct differences in the cells of the three germ bands and various regions of the embryo. The posterior region (including the hindgut) expands and extends towards the anterior pole along the dorsal side of the embryo. The earliest signs of segmentation appear during this phase with the formation of ''parasegmental furrows''. This is also when the tracheal pits form, the first signs of structures for breathing. Germ band retraction returns the hindgut to the dorsal side of the posterior pole and coincides with overt [[segmentation (biology)|segmentation]]. The remaining stages involve the internalization of the nervous system (ectoderm) and the formation of internal organs (mainly mesoderm). ==Anterior-posterior axis patterning in ''Drosophila''== One of the best understood examples of pattern formation is the patterning along the future head to tail (antero-posterior) axis of the fruit fly ''[[Drosophila melanogaster]]''. The development of ''Drosophila'' is particularly well studied, and it is representative of a major class of animals, the insects or [[insecta]]. Other multicellular organisms sometimes use similar mechanisms for axis formation, although the relative importance of signal transfer between the earliest cells of many developing organisms is greater than in the example described here. ===Maternal effect genes=== {{Further|[[Maternal effect]]}} [[Image:Maternal effect mRNAs.png|frame|Figure 1. mRNA distributions.]] [[Image:Drosophila early embryo protein gradients.png|frame|right|Figure 2. Protein distributions.]] The building-blocks of anterior-posterior axis patterning in ''Drosophila'' are laid out during egg formation ([[oogenesis]]), well before the egg is fertilized and deposited. The developing egg ([[oocyte]]) is polarized by differentially localized [[mRNA]] molecules. The genes that code for these mRNAs, called '''maternal effect genes''', encode for proteins that get translated upon fertilization to establish concentration gradients that span the egg. ''Bicoid'' and ''hunchback'' are the maternal effect genes that are most important for patterning of anterior parts (head and thorax) of the ''Drosophila'' embryo. ''Nanos'' and ''Caudal'' are maternal effect genes that are important in the formation of more posterior abdominal segments of the ''Drosophila'' embryo. [[cytoskeleton|Cytoskeletal]] elements such as [[microtubule]]s are polarized within the oocyte and can be used to allow the localization of mRNA molecules to specific parts of the cell. Maternally synthesized ''bicoid'' mRNAs attach to microtubules and are concentrated at the anterior ends of forming ''Drosophila'' eggs. ''Nanos'' mRNAs also attach to the egg cytoskeleton but they concentrate at the posterior ends of the eggs. ''Hunchback'' and ''caudal'' mRNAs lack special location control systems and are fairly evenly spread throughout the interior of egg cells. When the mRNAs from the maternal effect genes are [[Translation|translated]] into proteins a Bicoid protein gradient forms at the anterior end of the egg. Nanos protein forms a gradient at the posterior end. The Bicoid protein blocks translation of ''caudal'' mRNA so Caudal protein is made only in the posterior part of the cell. Nanos protein binds to the ''hunchback'' mRNA and blocks its translation in the posterior end of ''Drosophila'' embryos. The Bicoid, Hunchback, and Caudal proteins are [[transcription factors]]. Bicoid has a DNA-binding [[Homeobox|homeodomain]] that binds both DNA and the ''nanos'' mRNA. Bicoid binds a specific RNA sequence in the [[3' UTR|3' untranslated region]] of ''caudal'' mRNA and blocks translation. Hunchback protein levels in the early embryo are significantly augmented by new ''hunchback'' gene transcription and translation of the resulting [[zygote|zygotically]] produced mRNA. During early ''Drosophila'' embryogenesis there are nuclear divisions without cell division. The many nuclei that are produced distribute themselves around the periphery of the cell cytoplasm. Gene expression in these nuclei is regulated by the Bicoid, Hunchback, and Caudal proteins. For example, Bicoid acts as a transcriptional activator of ''hunchback'' gene transcription. [[Image:bicoid gradient.png|frame|left|Figure 3. bicoid gradient]] [[Image:nanos gradient.png|frame|right|Figure 4. nanos gradient]] {{-}} ===Gap genes=== [[Image:Gap ene expression.png|frame|right|Figure 5. Gap genes.]] The other important function of the gradients of Bicoid, Hunchback, and Caudal proteins is in the transcriptional regulation of other zygotically expressed proteins. Many of these are the protein products derived from members of the "gap" family of developmental control genes. ''Hunchback'', ''krüppel'', ''giant'', ''tailless'' and ''knirps'' are all '''gap genes'''. Their expression patterns in the early embryo are determined by the maternal effect gene products and shown in the diagrams on the right side of this page. The gap genes are part of a larger family called the '''segmentation genes'''. These genes establish the segmented body plan of the embryo along the anterior-posterior axis. The segmentation genes specify 14 "parasegments" that are closely related to the final anatomical segments. The gap genes are the first layer of a hierarchical cascade of the segmentation control genes. Proteins such as Bicoid can be described as morphogens that act within the [[Syncytium|syncytial]] blastoderm of the early ''Drosophila'' embryo. These intracellular morphogens enter the nuclei and act as transcription factors to control expression of the gap genes. In the blastoderm stage of ''Drosophila'' morphogenesis four types of nuclear specification can be distinguished: *Anterior (head and thorax) *Posterior (abdomen) *[[Dorsum (biology)|Dorso]]-[[ventral]] *Terminal (special structures at the unsegmented ends of the embryo) ===Additional segmentation genes=== [[Image:Pair rule.jpg|frame|Figure 6. Pair rule.]] Two additional classes of segmentation genes are expressed after the gap gene products. The '''pair-rule genes''' are expressed in striped patterns of seven bands perpendicular to the anterior-posterior axis (see Figure 6, ''even-skipped''). These patterns of expression are established within the syncytial blastoderm. After these initial patterning events, cell membranes form around the nuclei of the syncytial blastoderm converting it to a cellular blastoderm. [[Image:Wingless.png|frame|Figure 7. Reciprocal signaling between Wingless and Hedgehog producing cells.]] The expression patterns of the final class of segmentation genes, the '''segment polarity genes''', are then fine-tuned by interactions between the cells of adjacent parasegments (see the example, ''engrailed'', Figure 7). The '''Engrailed''' protein is a transcription factor (yellow in Figure 7) that is expressed in one row of cells at the edge of each parasegment. This expression pattern is initiated by the pair-rule genes (like ''even-skipped'') that code for transcription factors that regulate the ''engrailed'' gene's transcription in the syncytial blastoderm. Cells that make Engrailed can make the cell-to-cell signaling protein '''[[Hedgehog (cell signaling)|Hedgehog]]''' (green in Figure 7). Hedgehog is not free to move very far and activates a thin stripe of cells adjacent to the Engrailed-expressing cells. Only cells to one side of the Engrailed-expressing cells are competent to respond to Hedgehog because they express the receptor protein '''Patched''' (blue in Figure 7). Cells with activated Patch receptor make the '''Wingless''' protein (red in Figure 7). Wingless protein acts on the adjacent rows of cells by activating its cell surface receptor, '''Frizzled'''. Wingless also acts on Engrailed-expressing cells to stabilize Engrailed expression after the cellular blastoderm forms. The reciprocal signaling by Hedgehog and Wingless stabilizes the boundary between each segment. The Wingless protein is called "wingless" because of the [[phenotype]] of some ''wingless'' mutants. Wingless also functioned during [[Metamorphosis_(biology)|metamorphosis]] to coordinate wing formation. The transcription factors that are coded for by segmentation genes regulate yet another family of developmental control genes, the '''homeotic selector genes'''. These genes exist in two ordered groups on ''Drosophila'' chromosome 3. The order of the genes on the chromosome reflects the order that they are expressed along the anterior-posterior axis of the developing embryo. The Antennapedia group of homeotic selector genes includes ''labial'', ''antennapedia'', ''sex combs reduced'', ''deformed'', and ''proboscipedia''. Labial and Deformed proteins are expressed in head segments where they activate the genes that define head features. Sex-combs-reduced and Antennapedia specify the properties of thoracic segments. The bithorax group of homeotic selector genes control the specializations of the third thoracic segment and the abdominal segments. In [[1995]], the [[Nobel Prize for Physiology or Medicine]] was awarded for studies concerning the genetic control of early embryonic development to [[Christiane Nüsslein-Volhard]], [[Edward B. Lewis]] and [[Eric F. Wieschaus|Eric Wieschaus]]. Their researches on genetic screening for embryo patterning mutants revealed the role played in early embryologic development by ''[[Homeobox gene]]s'' like ''bicoid''. An example of a homeotic mutation is the so-called antennapedia mutation. In ''Drosophila'', antennae and legs are created by the same basic "program", they only differ in a single transcription factor. If this transcription factor is damaged, the fly grows legs on its head instead of antennae. See images of this "antennapedia" mutant and others, at [http://flybase.bio.indiana.edu FlyBase]. ==Tools== [[Mutagenesis]] allow scientists to disrupt the function of genes in the fly. This is useful for studying embryogenosis. It is fairly easy for an experienced scientist to make [[Genetically modified organism|transgenic flies]]. This is a very useful tool and opens up many possibilities. It allows the study of the role of the gene in embryogenosis. It is possible to tag a fly protein with a fluorescent protein such as [[green fluorescent protein]] (GFP). This means that you can watch the dynamics of the localisation of that protein. It is even possible to do so in living organisms. The fly genome has been published and is an extremely useful resource. It can be used to look for the [[homology (biology)|homolog]] of genes from other organisms, that are involved in embryogenosis. Once such a gene has been identified in fly it will make the study of its function possible and increase the understanding of the role of the gene product. ==See also== *[[Morphogenesis]] *[[Pattern formation]] ==External links== *Fly Move: http://flymove.uni-muenster.de *The Interactive Fly: http://www.sdbonline.org/fly/aimain/1aahome.htm [[Category:Developmental biology]] [[Category:Entomology]] [[Category:Drosophilidae]] [[es:Embriogénesis en Drosophila]]