Public Affairs
Baylor College
of Medicine
One Baylor Plaza,
Room 176B
Houston, TX 77030
Telephone:
  (713) 798-4712
Fax:
  (713) 798-3692
email: pa@bcm.tmc.edu

Photos Available Upon Request

Comments, Suggestions?

The frog: A prince among model organisms for developmental biologists

by Kate Ramsayer

(Editor’s Note: This is one in an occasional series of articles spotlighting the organisms important in a variety of biological studies.)

With no natural enemies and an uncanny ability to tolerate hostile environments, frogs of the species Xenopus laevis lord over the ponds of South and Central Africa. Their skin contains a toxin that wards off potentially predatory birds and fish and also produces antibacterial and antiviral compounds that prevent the amphibians from getting infections, even in the dirtiest of waters.

The frogs eat anything and everything smaller than they are, about 5 inches long. When the food runs out, they hop over to the next pond.

Xenopus - used with permission Carolina Biological Supply Co.

For over 100 years now, many of these frogs have found a new home in developmental and cell biology laboratories around the world. Originally, Xenopus was used as a pregnancy test. When female frogs were injected with the urine of a pregnant woman, a hormone caused them to lay eggs the next day.

Once fertility scientists moved on to other methods of detecting pregnancy, however, biologists realized the potential for these frogs in the studies of embryonic development. The embryos are not only relatively large (approximately a millimeter in diameter) but grow outside of the mother. These characteristics make it easy for the scientists to study the continuous divisions and developments of embryos.

The first Nobel Prizes awarded for developmental biology research went to Hans Spemann, PhD, in 1935 for his work in discovering a certain cluster of cells in an amphibian embryo, now called the Spemann Organizer. This cluster, when transplanted to another side of the embryo, can organize the cells around it to form a secondary embryo.

“That really initiated some incredible research into how gastrulation, neurulation, and pattern formation works,” said Milan Jamrich, PhD, an associate professor at Baylor College of Medicine's department of molecular and cellular biology, who has worked with Xenopus for 20 years.

Gastrulation is a crucial time in the development of multicellular animals. During gastrulation, the layers that become tissue types are established along with the basic body plan. Neurulation creates the neural tube that is the beginning of the central nervous system, the neural crest that gives rise to a diverse set of cell types and the bona fide epidermis that covers over the newly created neural tube.

Thousands of embryos

Milan Jamrich, PhD

Beyond their size and ease of access, frog embryos are advantageous to researchers because they can be cheaply and easily mass-produced.

If researchers want to study early embryo development, all they have to do is inject human chorionic gonadotropin hormone (the same hormone found in pregnant woman’s urine) into a female frog. The next day, they gently squeeze the frog, which will produce hundreds or thousands of eggs. Researchers can fertilize these eggs all at once, in order to get a large number of embryos that divide and grow as a synchronous population.

“If we wanted to collect thousands of embryos in frogs, it just takes one to two days, and would cost us two or three dollars,” said Jamrich. “If we did that in mice, it would take months and cost us thousands and thousands of dollars. That’s a particular advantage of looking at early development in frogs.”

And while researchers can observe Xenopus embryos unobtrusively under a microscope, researchers studying mouse embryos need to sacrifice both the mother and the embryo to study it.

While frogs are a good model for studying early embryonic development, they aren’t as useful in other areas, such as genetics. Although Xenopus embryos are quick to hatch into tadpoles, it takes a year for a tadpole to become a sexually mature frog. Because of this, if a scientist has a frog with a mutation that she wants to study, she would have to wait a year before she could cross that frog with others to investigate the mutation further.

Some researchers are trying to get around this problem by using a different species of frog, called Xenopus tropicalis. Instead of taking a year to reach sexual maturity like X. laevis, the smaller X tropicalis takes only four months.

To make an eye

At BCM, Jamrich takes advantage of a unique characteristic of frog embryos to study vertebrate pattern formation – the process in which the body plan of an animal is laid out, and one group of cells decides to make a tail, while another decides to make a heart or the brain or an eye.

For the first 7 hours of an embryo's life, however, it only makes proteins from genes that were already active in the mother's egg, called maternal genes. Only after that point does the embryo start making proteins from its own genome. Three hours later, the embryo starts to differentiate into the groups of cells destined to become one specific part of the tadpole.

With this information, researchers can assume the genes that were active during those three hours have important roles to play in directing the fate of the cells that will become organs and specialized systems.

Those genes "must be the earliest genes that tell the embryo to change its shape and to develop new cell types," said Jamrich. He and his colleagues identified one of these early genes called Rx, which is short for retinal homeobox.

"We found a gene we think to be a key component in the development of the eye," said Jamrich. "If this gene is mutated to a degree that it is not functional, frogs or in fact vertebrates of any kind do not develop eyes."

Jamrich's lab has demonstrated this phenomenon by putting in a special nucleotide or genetic sequence called an antisense morpholino, which binds to the Rx messenger RNA and prevents it from forming a protein. Without the Rx protein, tadpoles don't have eyes.

The scientists are also studying how Rx protein is present only in the retina, and looking into how amphibians can regenerate parts of a damaged eye, while other vertebrates cannot.

While kissing a frog won't turn it into a prince anytime soon, the amphibians' observable and easily manipulated embryonic development make them invaluable for developmental and cell biologists everywhere.

© Copyright 2003 - 2004 Baylor College of Medicine. All Rights Reserved.