Normal neurulation in mammals.

During mammalian neurulation regional differences are evident between the cranial region, in which neurulation is most complex, the trunk as far as the caudal neuropore and the secondary neurulation region of the caudal trunk plus tail. Differences among these three regions are characterized by specific patterns of morphogenesis and by specific patterns of gene expression. During cranial neurulation distinct regions develop in the brain and the presomitic hindbrain forms seven rhombomeric divisions. The first clear morphological boundary is the preotic sulcus (later transformed into the gyrus between rhombomeres 2 and 3), which may limit cell movement as neuroepithelial cells rostral to it flow towards and into the rapidly expanding forebrain region. The formation of rhombomeres as morphological entities and the development of a normal rhombomere-specific pattern of homeobox and other gene expression domains depend on relatively low levels of retinoic acid. Retinoic acid receptors, which are retinoic acid-activated transcription factors, and retinoid binding proteins, which control the availability of retinoic acid to the receptors, show regional patterns of expression in the cranial, trunk and caudal regions of the neuroepithelium during neurulation. These patterns suggest a possible mechanism for region-specific gene expression during neurulation.