A Model of Morphogenesis in Drosophila
Target Age or Ability Group Audience
Teacher Instructions/Special Precautions
Materials & Equipment Needs
Background [Prior Knowledge
or vocabulary necessary to complete activity]
The Student Lab
Method of Evaluation/Assessment
In the sequence of mitotic divisions which result
in the single-celled zygote becoming a complete organism consisting of
trillions of cells, three main processes are involved. The three components
of embryonic development are cell division, differentiation, and morphogenesis.
After the zygote is formed, growth and development
occurs through mitotic divisions. Differentiation allows cells with identical
chromosomes to express different genes, thereby giving rise to specialized
cells responsible for an organism's development.
Morphogenesis involves the movement, arrangement
and differentiation of cells during early development to produce
a 3D body shape. In embryonic development, a sequence of events takes place
that establishes the basic body plan of the animal.
An important premise about cell differentiation during
development is that at fertilization the egg is not uniform in its chemical
makeup. The side opposite from where the sperm penetrates has a high concentration
of Ca++. The distribution of mRNA's within the cell is also uneven. Hence,
when the cell divides the two new cells have different chemical/ molecular
concentrations that affect the expression of their genes in a unique manner.
The molecular difference between cells may be great enough to suppress
or activate the expression of genes in one cell and inhibit them
How cells differentiate has been a major question
among developmental biologists. The discovery of morphogens, often
described as growth factors, has helped to answer some of these questions.
The first morphogens were isolated around 20 years ago. The most studied
in the Drosophila appear to be the bicoid, nanos,
and hunchback, Dpp, hedgehog. These are responsible
for anterior, posterior, and the banding pattern in the midsection. Cells
determine their location in the embryo by detecting concentration gradients
of the different morphogens.
Cells in the center of the embryo, for example,
determine their position because the anterior and posterior morphogens
are of equal concentration at the midsection. If the concentration of the
first was slightly higher than that of the second, then the cells determine
their location in the larva as anterior to the midsection. In order to
fine tune their location as development progresses, more tissues produce
such molecules and the concentration of these morphogens helps to give
each tissue a precise reference to its position in the body. Morphogens
may also help in inducing genes that help the cells differentiate. This
activity focuses on the role morphogens have on development, even tough
other factors are involved.
The purpose of this exercise is to help students
understand the concept of how varying concentration gradients aid
the cells in locating their position in the embryo.
The effect of morphogens is based on their concentration
in the cells, which is regulated by: (1) The rate of diffusion,
which involves how fast the morphogen can get to the target cells (a function
of distance) , (2) The rate at which it decays. The stability of
the molecule and presence of chemicals that may degrade it are important
factors that affect this rate. (3) The reaction. The morphogen may
have to be over a threshold level concentration to trigger an effect on
gene expression in a given cell.
During early gastrulation, bicoid
expresses two genes that cause the striping of the larva. Bicoid
protein arises from mRNA at the anterior end pole of the egg. Following
fertilization these mRNA's are translated and the proteins diffuse posteriorly
to form a gradient beyond the midpoint of the larva. This gradient helps
to organize the body's segmentation. It appears that each cell nucleus
measures the exact concentration of bicoid protein and directly reads the
slope of the gradient. Bicoid drives high levels of hunchback
protein transcription and then binds it to specific regulatory genes in
target zones. The protein products of the regulatory genes form local concentrations
gradients, which control the transcription of genes further down the hierarchy.
Each cell layer has a definite anterior-posterior orientation. Following
this event, the dorsal-ventral orientation divides the embryo like
a checkerboard. Each would be a parasegment responsible for generating
a precise region of the larva and adult. Cells from neighboring compartments
will have different affinities, and tend to minimize their mutual contact
to limit cell movement between them. Thus, when a signal does cross over
the border into the next square, all the cells within range are affected.
Evidence suggests that Dpp is a long range
morphogen produced in the anterior end of each compartment. Dpp
is triggered by the release of the hedgehog which is produced in
the posterior region of the previous compartment. Hedgehog appears
to be a short-range inducer to elicit a long-range morphogen (Dpp).
The concentration landscape of the morphogen gradients
contains three types of information. The scalar concentration provides
positional information about how far a given cell is from the peak. The
direction of maximal change provides information about orientation with
respect to the source. The slope of the gradient relates to the size of
Although we discussed the Drosophila model
exclusively, there are examples of vertebrate morphogens, such as activin.
This protein can determine the cell state in mesodermal cells.
At the end of the lab, students should be able to:
Determine rates of diffusion.
Analyze and graph data.
Describe the role of morphogens in the development of the larva.
Explain the chemical dynamics of a cell, and its influence on the cell's
Understand the significance of embryo polarity during development.
Target Audience or Age Group
Grade level: 6-12
Biology, Anatomy and Physiology, Genetics
Notes to the Teacher:
Before the lab, the teacher must prepare the models of
Roll out the modeling clay so that it is 1/4" thick.
Using the fuel tank in a kit from an inexpensive model airplane kit ( 2"-3"),
make as many molds as you have teams (you may want to use this mold over
the years, so make as many molds as you need for large classes). A battery
(AA) works in making a mold.
Pour 2% agar into the molds to make a model of the Drosophila larva.
After the larva models have solidified, place them in a zip lock bag and
keep refrigerated until lab time. Be careful not to break them as they
Materials & Equipment
Needs to top
Fuel tank from a model plane, or a AA battery
Food coloring (red, yellow, and blue)
Zip lock bags
3 pieces of filter paper (size: 1/4" x 3/4")
[Prior Knowledge or Vocabulary Necessary to Complete Activity]
The significance of embryo polarity during cleavage.
The early stages of embryogenesis (from the unequal distribution of the
chemicals found in the cytoplasm of the egg to the formation of the larvae).
The concept of chemical gradient.
The process of diffusion.
Lab to top
From the instructor, obtain your model of
the Drosophila larvae. Place it in an open petri dish. With a razor,
slice 1/4 inch from each end deep into the model and once exactly in the
center. In the incision, place a piece of filter paper soaked in the appropriate
dye (use forceps to insert the paper into the cut). The red dye should
be added to the end you want to represent the anterior end of the larva
representing the bicoid morphogen. The blue dye should be added
to the posterior end of the larva representing the nanos morphogen.
Place the yellow dye in the middle of the larva representing the hunchback
morphogen. Trim the paper so that it is just sticking out the larva.
After 20 minutes, when the dye has been absorbed,
remove the filter papers.
Write your name on a strip of masking tape and place
it around the side of the petri dish. Give the larva back to you instructor
to keep in the refrigerator.
The second day, get your larva from your teacher
and place the petri dish on top of a sheet of paper.
Determine the length of your larva, and the distance that the red, blue,
and yellow dyes diffused.
Identify the different colors you observe after complete diffusion
has occurred. Because the two colors from the ends merge with yellow in
the center, five colors result- red, orange, yellow, green , blue, representing
the five morphogens mentioned above. Determine from your data the rate
of migration of each individual dye.
Methods of Evaluation/Assessment
What is the rate of diffusion of the anterior morphogen (represented by
Graph the rate of migration of the individual dyes overtime.
Identify the dependent and independent variable in the above graph.
Identify the anterior, posterior, and midsection morphogens that have been
identified in Drosophila larvae (from the reading)
How might a cell determine its position in the embryo by use of a morphogen
What morphogen (in the Drosophila larvae) is represented by (1)
red, (2) blue, and (3) yellow?
What structures do you think will develop from: (1) red , (2) orange, (3)
yellow, (4) green, and (5) blue.
What happened to the concentration of the morphogen as it moved away from
the point of origin? Explain.
Do all the cells respond to the same concentration of a given morphogen
Do all cells respond to the same concentration of a given morphogen equally?
What kind of biological molecule is a morphogen? Hypothesize
about the the characteristics of the morphogen molecule in terms of
(1) size, (2) solubility, and (3) other structural characteristics that
allow the morphogen to perform its function. (ESSAY)
Cells identify their relative position by use of anterior and posterior
morphogens in the embryo. How can cells more accurately fine tune their
embryological position? (ESSAY)
Design an experiment that demonstrates the role of morphogen in differentiation
in the Drosophila larvae.
Have students make a colored drawing of the Drosophila larvae showing
the banding pattern. It may be helpful to have them look at photographs
of such pictures first. Pictures are found in the magazine "Cell" vol.
Suggest that students research anomalies found in Drosophila due
to errors in development caused by the lack of morphogens, timing of morphogen
References Including Web Addresses
Morphogens, Compartments, and Pattern: Lessons from Drosophila?
Lawrence, Struhl, 1996. Cell, Vol.85, 951-961, June 28,1996.
The Biology Project, University of Arizona, November 8, 1996. URL
Reaction-Diffusion, Ingo K. Hunsinger, 1996.
URL address: http://www.informatik.uni-bremen.de/~ingo/Publications/tos/node3.html
Toward an Evolvable Model of Development Autonomous Agent Synthesis,
Dellaert and Beer, 1996. URL address: ftp://alpha.ces.cwru.edu/pub/agents/dellaert/alife/alife.html
Manipulating the anteroposterior pattern of the Drosophila embryo,
Frohnhofer, Lehmann, Nusslein-Volhard, 1986. Journal of Embryology,
97 Supplement, 169-179.
Synergy between the Hunchback and Bicoid Morphogens is Required for
Anterior Patterning in Drosophila, Simpson-Brose, Treisman, Despain,
1994. Cell, Vol.78, 855-865, September 9, 1994.
Vanessa Bishop, Phil Talbot