Developmental Biology of Drosophila

DROSOPHILA DROSOPHILA DEVELOPMENDEVELOPMEN

TTArun Kumar PradhanArun Kumar Pradhan

ONAONA

Odisha NET Academy ONA 09337727724Odisha NET Academy ONA 09337727724

DEVELOPMENTDEVELOPMENT An organism arises from a fertilized egg as the An organism arises from a fertilized egg as the

result of three related processesresult of three related processes• Cell divisionCell division• Cell differentiationCell differentiation• MorphogenesisMorphogenesis


DIFFERENTIATIONDIFFERENTIATION Cells may initially remain undifferentiatedCells may initially remain undifferentiated

• Embryonic stem cellsEmbryonic stem cells Cells ultimately Cells ultimately

differentiatedifferentiate• Become specialized in Become specialized in

structure and functionstructure and function


DIFFERENTIATIONDIFFERENTIATION Virtually all cells within a multicellular Virtually all cells within a multicellular

organism are genetically identicalorganism are genetically identical Differences between cells are due to differences Differences between cells are due to differences

in gene expressionin gene expression• Different subsets of genes are “on” and “off”Different subsets of genes are “on” and “off”• Different cell types make different proteinsDifferent cell types make different proteins


GENE EXPRESSIONGENE EXPRESSION Much of the regulation of gene expression Much of the regulation of gene expression

occurs at the level of transcriptionoccurs at the level of transcription Transcriptional regulation Transcriptional regulation

of gene expression is of gene expression is directed bydirected by• Maternal molecules in the Maternal molecules in the

cell’s cytoplasmcell’s cytoplasm• Signals from other cellsSignals from other cells


PATTERN FORMATIONPATTERN FORMATION The development of a spatial organization in The development of a spatial organization in

which an organism’s tissues and organs are all in which an organism’s tissues and organs are all in their characteristic placestheir characteristic places

In animals, it begins in early embryoIn animals, it begins in early embryo• Basic body plan is establishedBasic body plan is established• Major axes are established earlyMajor axes are established early

Studied most extensively in Studied most extensively in Drosophila Drosophila melanogastermelanogaster


Drosophila melanogasterDrosophila melanogaster Bilaterally symmetric segmented bodyBilaterally symmetric segmented body

• HeadHead• ThoraxThorax• AbdomenAbdomen


Drosophila melanogasterDrosophila melanogaster Cytoplasmic determinants are present in the Cytoplasmic determinants are present in the

unfertilized eggunfertilized egg• Provide positional information for placement of axes Provide positional information for placement of axes

prior to fertilizationprior to fertilization• Establishes number and orientation of segmentsEstablishes number and orientation of segments• Ultimately trigger formation of specific structures Ultimately trigger formation of specific structures

within each segmentwithin each segment


Drosophila melanogasterDrosophila melanogaster Egg develops in mother’s ovaryEgg develops in mother’s ovary

• Surrounding cells with nutrients, etc.Surrounding cells with nutrients, etc. Mitosis begins following fertilizationMitosis begins following fertilization

• First ten divisions include no growth, cytokinesisFirst ten divisions include no growth, cytokinesis• Single multinucleate cell resultsSingle multinucleate cell results


Drosophila melanogasterDrosophila melanogaster Nuclei migrate to periphery of embryo at tenth Nuclei migrate to periphery of embryo at tenth

divisiondivision Plasma membranes finally partition ~6,000 Plasma membranes finally partition ~6,000

nuclei into separate cells at the thirteenth nuclei into separate cells at the thirteenth divisiondivision• Basic body plan already Basic body plan already

determined at this timedetermined at this time Body axes and segment Body axes and segment

boundariesboundaries


Drosophila melanogasterDrosophila melanogaster Subsequent embryonic events create clearly Subsequent embryonic events create clearly

visible segmentsvisible segments• Initially look very similarInitially look very similar

Some cells move to new Some cells move to new positionspositions• Organs formOrgans form

Wormlike larva hatchesWormlike larva hatches• Eats, grows, & moltsEats, grows, & molts


Drosophila melanogasterDrosophila melanogaster Larva eventually forms a Larva eventually forms a

pupapupa• Enclosed in a caseEnclosed in a case

Metamorphosis occursMetamorphosis occurs• Change from larva to adult flyChange from larva to adult fly

Adult fly emerges from caseAdult fly emerges from case• Each segment is anatomically Each segment is anatomically

distinctdistinct


Drosophila melanogasterDrosophila melanogaster Each segment in the adult fly is anatomically Each segment in the adult fly is anatomically

distinctdistinct• Characteristic appendagesCharacteristic appendages


Drosophila melanogasterDrosophila melanogaster Gradients of maternal molecules in the early Gradients of maternal molecules in the early

embryo control axis formationembryo control axis formation• Cytoplasmic determinants already present in Cytoplasmic determinants already present in

unfertilized eggunfertilized egg• Encoded by mother’s Encoded by mother’s maternal effect genesmaternal effect genes

a.k.a., “a.k.a., “Egg-polarity genesEgg-polarity genes”” Encode proteins or mRNAs that are placed into the egg Encode proteins or mRNAs that are placed into the egg

while still in the mother’s ovarywhile still in the mother’s ovary


Drosophila melanogasterDrosophila melanogaster One group of maternal effect genes establishes One group of maternal effect genes establishes

the anterior-posterior axis of the embryothe anterior-posterior axis of the embryo Another set of maternal effect genes establishes Another set of maternal effect genes establishes

the dorsal-ventral axisthe dorsal-ventral axis

Female flies possessing mutations in Female flies possessing mutations in maternal maternal effect geneseffect genes appear phenotypically normal, but appear phenotypically normal, but produce offspring with mutant phenotypesproduce offspring with mutant phenotypes


Drosophila melanogasterDrosophila melanogaster BicoidBicoid is an egg-polarity gene is an egg-polarity gene

• ““Two-tailed”Two-tailed” Mothers defective in Mothers defective in bicoidbicoid produce embryos produce embryos

lacking the front half of their bodylacking the front half of their body• Duplicate posterior structure at both endsDuplicate posterior structure at both ends


Drosophila melanogasterDrosophila melanogaster BicoidBicoid gene product is concentrated at anterior gene product is concentrated at anterior

end of fly embryoend of fly embryo• Gradient of gene productGradient of gene product• Essential for setting Essential for setting

up anterior end of flyup anterior end of fly

Gradients of other proteins Gradients of other proteins determine the posterior end determine the posterior end and the dorsal-ventral axisand the dorsal-ventral axis


The bicoid gradient regulates the expression of The bicoid gradient regulates the expression of segmentation genes in a concentration-segmentation genes in a concentration-

dependent fashion.dependent fashion.

There are peak levels of theThere are peak levels of the

Bicoid protein in anteriorBicoid protein in anterior

regions, intermediate levels inregions, intermediate levels in

certral regions, and low levelscertral regions, and low levels

in posterior regionsin posterior regions..

OrthodenticleOrthodenticle is activated only is activated only

by high levels of the Bicoidby high levels of the Bicoid

gradient in the head;gradient in the head;

hunchbackhunchback is activated by both is activated by both

high and intermediate levels inhigh and intermediate levels in

the head and thorax.the head and thorax.Odisha NET Academy ONA 09337727724Odisha NET Academy ONA 09337727724

In central In central regions of the regions of the embryo, the embryo, the

orthodenticle orthodenticle gene is off. In gene is off. In

contrast, contrast, hunchback hunchback is is on. These is on. These is

control by the control by the levels of Bicoid levels of Bicoid

protein.protein.Odisha NET Academy ONA 09337727724Odisha NET Academy ONA 09337727724

Hunchback expression is also Hunchback expression is also regulated at the level of regulated at the level of

translationtranslationThe translation is blocked in posterior regions by The translation is blocked in posterior regions by

RNA-binding protein called RNA-binding protein called NanosNanos. . After the After the NanosNanos mRNA is translated, the protein diffuses from mRNA is translated, the protein diffuses from posterior regions to form a gradient. The translation of posterior regions to form a gradient. The translation of the maternal the maternal hunchbackhunchback mRNA is arrested by the mRNA is arrested by the Nanos protein. The Nanos gradient thereby leads to the Nanos protein. The Nanos gradient thereby leads to the formation of a reciprocal Hunchback gradient in formation of a reciprocal Hunchback gradient in anterior regions.anterior regions.


Hunchback and gapHunchback and gap proteins produce segmentation stripes of proteins produce segmentation stripes of

gene expression.gene expression.


Drosophila melanogasterDrosophila melanogaster The The bicoidbicoid protein and the products of other protein and the products of other

egg-polarity genes are egg-polarity genes are transcription factorstranscription factors• Regulate the expression Regulate the expression

of some of the embryo’s of some of the embryo’s genesgenes


Drosophila melanogasterDrosophila melanogaster Segmentation genesSegmentation genes

• Genes of embryoGenes of embryo• Expression regulated by products of egg-polarity Expression regulated by products of egg-polarity

genesgenes• Direct the actual formation of segments after the Direct the actual formation of segments after the

embryo’s major axes are definedembryo’s major axes are defined


Drosophila melanogasterDrosophila melanogaster Three sets of segmentation genes are activated Three sets of segmentation genes are activated

sequentiallysequentially• Gap genesGap genes• Pair-rule genesPair-rule genes• Segment polarity genesSegment polarity genes

The activation of these sets of genes defines the The activation of these sets of genes defines the animal’s body plananimal’s body plan• Each sequential set regulates increasingly fine detailsEach sequential set regulates increasingly fine details


Drosophila melanogasterDrosophila melanogaster Gap genesGap genes

• Map out basic subdivisions along the embryo’s Map out basic subdivisions along the embryo’s anterior-posterior axisanterior-posterior axis

• Mutations cause “gaps” in the animal’s segmentationMutations cause “gaps” in the animal’s segmentation


Drosophila melanogasterDrosophila melanogaster Pair-rule genesPair-rule genes

• Define pattern in terms of pairs of segmentsDefine pattern in terms of pairs of segments• Mutations result in embryos having half the normal Mutations result in embryos having half the normal

number of segmentsnumber of segments


Drosophila melanogasterDrosophila melanogaster Segment polarity genesSegment polarity genes

• Set the anterior-posterior Set the anterior-posterior axis of each segmentaxis of each segment

• Mutations produce Mutations produce segments where part of the segments where part of the segment mirrors another segment mirrors another part of the same segmentpart of the same segment


Drosophila melanogasterDrosophila melanogaster The products of many of the segmentation genes The products of many of the segmentation genes

are transcription factorsare transcription factors• Directly activate the next set of genesDirectly activate the next set of genes

SummarySummary• Products of the egg-polarity genes regulate the Products of the egg-polarity genes regulate the

regional expression of the gap genesregional expression of the gap genes• Gap genes control the localized expression of the Gap genes control the localized expression of the

pair-rule genespair-rule genes• Pair rule genes activate specific segment polarity Pair rule genes activate specific segment polarity

genes in different parts of each segmentgenes in different parts of each segment• Segment polarity genes activate homeotic genesSegment polarity genes activate homeotic genes


HOMEOTIC GENESHOMEOTIC GENES Master regulatory genesMaster regulatory genes Specify the types of appendages and other Specify the types of appendages and other

structures that each segment will formstructures that each segment will form Mutations produce flies with structures in Mutations produce flies with structures in

incorrect placesincorrect places


HOMEOTIC GENESHOMEOTIC GENES Encode transcription factorsEncode transcription factors Control the expression of genes responsible for Control the expression of genes responsible for

specific anatomical structuresspecific anatomical structures• e.g., “Antennae go here”e.g., “Antennae go here”• e.g., “Legs go here”e.g., “Legs go here”


HOMEOTIC GENESHOMEOTIC GENES Homeotic genes are Homeotic genes are

master genes that master genes that regulate the regulate the expression of expression of numerous other genesnumerous other genes• Some of the regulated Some of the regulated

genes are regulatory genes are regulatory themselvesthemselves


DrosophilaDrosophila DEVELOPMENT DEVELOPMENTHierarchy of Gene ActivityHierarchy of Gene Activity Maternal genesMaternal genes Segmentation genes of embryoSegmentation genes of embryo

• Gap genesGap genes• Pair-rule genesPair-rule genes• Segment polarity genesSegment polarity genes

Homeotic genes of the embryoHomeotic genes of the embryo Other genes of the embryoOther genes of the embryo


HOMEOTIC GENESHOMEOTIC GENES Homeotic genes of Homeotic genes of DrosophilaDrosophila all possess all possess

homologous segmentshomologous segments• 180-nucleotide sequence = 180-nucleotide sequence = homeoboxhomeobox• Encodes 60-amino-acid Encodes 60-amino-acid homeodomainhomeodomain

Homologous sequences have been found in Homologous sequences have been found in many other animalsmany other animals• e.g., Insects, nematodes, mollusks, fish, frogs, birds, e.g., Insects, nematodes, mollusks, fish, frogs, birds,

humans, etc.humans, etc.• Related genes are even found in yeast, etc.Related genes are even found in yeast, etc.• HoxHox genes genes


HOMEOTIC GENESHOMEOTIC GENES Vertebrate genes Vertebrate genes

homologous to the homologous to the homeotic genes of homeotic genes of DrosophilaDrosophila have have maintained their maintained their chromosomal chromosomal arrangementarrangement


Thank you


Science

Developmental Biology of Drosophila