John and Heather Pipiens were very nervous. Heather had recently given birth to a good-sized clutch of eggs. Most of the little larvae were doing fine. The one exception was Barney. His head development was not like the rest of his siblings. His head seemed smaller than it should be, and he hadn’t formed his adhesive glands yet.
“What do you think could be wrong?” asked Heather, who looked very worried.
“Don’t get all worked up,” replied John. “I am sure it’s nothing. He just may be a little slower than the rest of the kids. We have 133 perfectly normal, healthy little larvae and not all of them developed at the exact same rate. Remember Gracie? She gastrulated almost a day later than the rest and she’s just fine. And Jason didn’t have his first cleavage until almost an hour after the others, and he’s doing great.”
Just then the nurse came out and called their name. They were escorted into an examination room. Barney’s height, weight, and somite count were taken. The nurse then told them that Dr. Triturus would see them in a few minutes.
True to her word, the doctor came into the exam room five minutes later. He took one look at Barney and his heart sank. He knew something was very wrong. He was definitely missing part of his forebrain and his entire adhesive gland. Based on his somite count, both should be very well developed by now.
Dr. Triturus turned and looked at the Pipiens and said, “Mr. and Mrs. Pipiens, at first glance there seems to be a problem with his developmental progress. He does have some head development abnormalities that I don’t believe are related to timing. Everything else seems to be okay; he has the correct number of somites for his age and his trunk seems to be developing just fine. The problem seems to be the front-most part of his head. It has failed to develop. I don’t know the exact cause just yet. I would like to admit him for some tests.”
“Is that really necessary?” asked Barney’s mom. “How serious is it? Can it be fixed?”
“I really can’t say at this time,” replied Dr. Triturus. “I need to do some tests to get a better idea of what is causing Barney’s problem before I can make a diagnosis. I would like you to leave him here over the weekend. You can pick him up on Monday.”
“But we want to stay with him,” said both his mom and dad.
“That really isn’t necessary. He is still in his jelly coat and not really aware of what is going on. Besides, you have 133 other children to take care of. Go home. He’ll be in good hands with us.”
John and Heather kissed Barney good-bye. The doctor had the nurse admit him and get him settled into his hospital tank. He then called his students together. Dr. Triturus had a pretty good idea of the cause of Barney’s problems but wanted to give his residents a chance at the diagnosis before he ran tests to confirm his hypothesis.
Dr. Triturus began, “We have a 4-day-old male anuran with abnormal head development. He is showing an absence of forebrain development and his adhesive glands have failed to form. Everything else seems to be normal. What are your thoughts?”
The med students looked at one other. Robert thought it might be a problem with his Nieuwkoop center. Sarah thought it was probably a problem with his organizer. Karen told them that they both were wrong and it had to be a problem that occurred during neurulation. It was obvious that this group of students had no real idea of what was going on.
“You are on track, just not the right one. It’s a problem with dorsal-ventral axis formation. But it’s obvious that most of you don’t know much about the development of the central nervous system. Go home and do some research on this and be prepared to answer some questions during rounds tomorrow afternoon. I am disappointed about how little you seem to know about this subject. It is one of the first developmental decisions an embryo makes and one of its most important. Go do some research and be prepared to have better answers tomorrow.”
Dr. Triturus went over to Barney’s tank to check on him one more time. Satisfied that he would be all right until morning, Dr. Triturus went home hopeful that his students would be better prepared the next time they met. If not, some of them might find themselves cleaning tanks for the next two weeks.
You are part of Dr. Triturus’s research group. You really don’t want to clean hospital tanks for the rest of your residency. To prepare for tomorrow’s rounds, answer the following questions and be ready to provide a diagnosis of the cause of Barney’s head abnormalities. Be prepared to justify your reasoning.
1.What are the organizer and the Nieuwkoop center mentioned by Robert and Sarah?
2. Dr. Triturus indicated that Barney’s problem had something to do with dorsal-ventral axis formation. Establishment of the DV axis in amphibians is an example of conditional specification. In this type of development, a cell’s fate is determined by interactions between neighboring cells referred to as induction. What inductive events occur during DV axis formation in amphibians?
1. The organizer is a group of cells that play a critical role in embryonic development by controlling the patterning and differentiation of neighboring cells. The Nieuwkoop center is a specific region within the organizer that is responsible for establishing the dorsal-ventral axis during development.
2. During dorsal-ventral axis formation in amphibians, multiple inductive events occur. These include:
- Dorsalizing factors secreted from the Spemann organizer, such as Chordin and Noggin, inhibit the activity of BMP (bone morphogenetic protein) signaling, which promotes ventralization. This leads to the formation of a graded BMP activity along the DV axis.
- The graded BMP activity determines the pattern of ventral fates, with higher levels leading to ventral cell identities and lower levels leading to dorsal cell identities.
- Nodal signaling, another important pathway in DV axis formation, is activated by the dorsalizing factors secreted by the organizer. Nodal signaling is essential for establishing the dorsal-ventral gradient of BMP activity.
- The interaction between dorsal and ventral cells also plays a role in DV axis formation. Dorsal cells express Wnt antagonists, such as Dkk1 and Crescent, which inhibit Wnt signaling in ventral cells. This inhibition allows for the establishment of dorsal fates.
- BMP signal antagonists, such as Chordin and Noggin, are also involved in creating a gradient of BMP activity along the dorsal-ventral axis. These antagonists are secreted by the organizer and bind to BMPs, preventing their signaling and promoting dorsalization.
These inductive events work together to establish the dorsal-ventral axis and determine the fate of cells along this axis during embryonic development.