Before you had to cope with the mind–numbing drudgery of high school‚ before you had to write three midterms in a week‚ before you had to serve no–foam soy lattes to yuppies who treat you like a talking vending machine‚ you had to accomplish something even more difficult: you had to grow from a ball of cells into an elongated embryo without ending up ass–backwards.
“[Developing as an early embryo] is one of the hardest things you will ever have to do‚” says developmental biology grad student Mary Kubesh. “Considering its complexity‚ it’s amazing how often it actually succeeds.”
Biologists at U of T have uncovered a piece of the incredibly intricate puzzle of embryological development. Dr. Rudolf Winklbauer and his postdoctoral fellow Hiromasa Ninomiya found that the lengthening of the embryo‚ and the subsequent development of the spine‚ is intrinsically linked to the designation of the head and the tail at opposite ends. This discovery may aid in the treatment of diseases like cancer and spina bifida‚ a birth defect where part of the spine is formed outside of the body.
All animals start off as a single cell‚ the fusion of an egg and a sperm. This single cell divides‚ creating a sphere of cells shaped a bit like a basketball. Through a number of complicated shape changes‚ this sphere folds in on itself‚ expands and grows‚ and eventually turns into something resembling the adult animal. As the sphere folds in on itself groups of cells that are destined to grow into particular organs‚ muscles‚ and other structures are placed in their appropriate locations‚ and the stage is set for the embryo to grow into a full animal.
“You have thousands of cells‚ and they all have to know where to go and when to go there; all of these cell movements have to be coordinated‚” says Kubesh‚ giving an idea of just how complex the growth of an embryo is.
One of the most important changes that takes place as the sphere folds and grows is a process called convergent extension. The cells of the future spine and back muscles converge at the midline and interlink‚ creating a narrow band of tissue in the middle of the embryo’s back and extending the animal from a ball into an elongated shape.
Ninomiya and Winklbauer showed that the extension of the back is intrinsically tied to the establishment of which end of the animal will become the head and which end the tail.
When they took the soon–to–be back cells of a frog and mixed them up in a petri dish‚ the cells moved back to their original positions. “These cells know where they come from‚” said Dr. Winklbauer. Only once the cells were back in their original places‚ and the head to tail axis had been re–established‚ did the back stretch out.
Ninomiya and Winklbauer found that the expression of two genes determines the direction of the head to tail axis. One gene‚ called Xenopus Brachyury is expressed the most at the future tail‚ fading off towards the head. The other gene‚ called chordin‚ is expressed in the opposite manner: the most at the head‚ and the least at the tail.
This pattern of gene expression‚ which determines the “head or tail” identity of the back cells‚ also tells the cells to converge at the midline and extend the embryo (although this mechanism has yet to be determined). “So this is an elegant way to ensure that you always get the axis elongated in the right way‚ not perpendicular or at an angle; you always push the head away from the tail‚” said Winklbauer.
The intellectual credit‚ he noted‚ should be attributed to Ninomiya‚ the lead author of the study. Ninomiya was fascinated by the process of convergent extension even in his undergraduate days and has dedicated himself to studying it for the past several years.