In mice, on the other hand, we carry out functional analysis by genetics. We transgenically misexpress molecules, and inactivate or mutate genes by DNA recombination in ES cells. Proof of the power of these strategies comes from our finding that inactivating the pdx-1 homeobox gene abolishes pancreas formation in mice. Our finding led to the discovery of similar defects in newborn humans with pdx-1 mutations. Furthermore, in the Islets of Langerhans of the adult pancreas, PDX-1 is an essential regulator of insulin gene transcription, and a select set of other genes regulating cell function.
Different vertebrates have different numbers of nodal-related genes.
Nodal proteins are potent intercellular signaling molecules that induce alterations in cell fate, or in cell behaviours like migration. Particularly exciting is the recent discovery of the role Nodal signaling plays in vertebrates in the asymmetric placement of the internal organs, circulatory system formation, and previously unknown molecular differences between the left and right sides of the brain. We also found that a classical zebrafish mutant, cyclops, corresponds to a lesion in a nodal-related gene. This finding greatly modified current thinking on the timing and molecules involved in forming the neural tube floor plate, a centrally located strip of cells running down the CNS that is an organizing center for the various types of neurons. Xenopus nodal-related signaling is essential for mesendodermal patterning during early embryogenesis.