Lessons from a great developmental biologist

The announcement that Sir John Gurdon had been awarded the 2012 Nobel Prize for Medicine or Physiology was received with great joy by developmental biologists. It was a very special occasion because of his total dedication to science and turning the Golden Rule of western civilization – love your neighbor as yourself – into a reality in our field. This essay attempts to explain how John became such a great scientific benefactor, and to review some of his discoveries that are less well known than the nuclear transplantation experiments. A few personal anecdotes are also included to illustrate the profound goodness of this unique man of science.     

Overexpression of the Xenopus Tight-Junction Protein Claudin Causes Randomization of the Left–Right Body Axis

This study presents Xenopus claudin (Xcla), a tight-junction protein that is abundantly expressed in eggs and neuroectodermal precursors during early development. It was isolated via a differential screen for mRNAs enriched in microsomes in the Xenopus blastula. The Xcla protein contains four transmembrane domains and a carboxy-terminal cytoplasmic region with a putative PDZ-binding site. We show that this PDZ-binding site of Xcla is critical for its correct localization on the cell membrane and that a truncated form leads to delocalization of the tight-junction protein ZO-1. Overexpression of Xcla causes changes in the cell adhesion properties of blastomeres and leads to visceral situs randomization. The results suggest that left–right axial patterning is very sensitive to changes in regulation of cell–cell interactions and implicate a tight-junction protein in the determination of left–right asymmetry.     

A Hox 3.3-lacZ transgene expressed in developing limbs.

We describe transgenic mouse lines that express lacZ under the control of the Hox 3.3 Promoter II. The correct anterior boundary can be fixed by 3.6 kb of promoter DNA (plus 1.6 kb of 5' transcribed sequences), both in tissues of ectodermal and mesodermal origin. The posterior border, however, is not respected, and lacZ expression continues into the tail region. One line has particularly strong graded expression in the anterior proximal limb bud. Other lines, containing a shorter promoter fragment (0.6 kb), have ectopic expression in the head region, including one line that has expression in the anterior half of the retina. Such mouse lines make it possible to molecularly distinguish cells in regions of the embryo that look otherwise identical and may be useful in studying the establishment of molecular differences in the mouse embryo.