Although neural tube defects are a common congenital anomaly, their etiology is not known. Human studies have emphasized the pathology and epidemiology of the defects and suggest that in the majority of cases the etiology is multifactorial. Factors which appear possibly to be important are genetic predisposition, maternal illness, and fetal drug exposure. Animal studies have utilized naturally occurring neural tube defects and teratologically induced lesions. No animal model has been convincingly established as the equivalent of human neural tube defects. However, animal models have allowed investigation of the mechanisms of suggested human teratogens and determination of the pathogenesis of naturally occurring animal defects. Their most important contribution has been in furthering the understanding of the normal mechanisms of neural tube closure. It may be through this understanding that the etiology of human neural tube defects will be determined.

Neuromuscular junction (NMJ) is a cholinergic synapse where motor neurons elicit muscle contraction. Agrin and its coreceptors LRP4 and MuSK are critical for vertebrate NMJ formation. This paper reviews recent evidence for Wnts and Wnt signaling molecules in NMJ formation including a possible retrograde mechanism by muscle β-catenin. We also present data that Wnt3a, 7a, 8a and 10b could inhibit agrin-mediated AChR clustering. Together with the stimulating effect of Wnt9a, 9b, 10b, 11 and 16 on AChR clustering in the absence of agrin, these results suggest diverse roles for Wnt ligands in NMJ development.

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The enteric nervous system is believed to be derived solely from the neural crest cells. This is partly based on the belief that the neural crest cells are the sole neural tube-derived cells colonizing the gastrointestinal tract. However, recent studies have shown that after the emigration of neural crest cells an additional population of cells emigrate from the cranial neural tube. These cells originate in the ventral part of the hindbrain, emigrate through the site of attachment of the cranial nerves, and colonize a variety of developing structures including the gastrointestinal tract. This cell population has been named the ventrally emigrating neural tube (VENT) cells. We followed the fate of these cells in the gastrointestinal tract. Ventral hindbrain neural tube cells of chick embryos were tagged with replication-deficient retroviral vectors containing the LacZ gene, after the emigration of neural crest from this region. In control embryos, the viral concentrate was dropped on the dorsal part of the neural tube. Embryos were sacrificed from embryonic days 3-12 and processed for the detection of LacZ positive ventrally emigrating neural tube cells. These cells colonized only the foregut, specifically the duodenum and stomach. Immunostaining with the neural crest cell marker HNK-1 showed that they were HNK-1 negative, indicating that they were not derived from neural crest. Cells were detected in three locations: (1). the myenteric and submucosal plexus of the enteric nervous system; (2). circular smooth muscle cell layer; and (3). mucosal lining of the lumen. A variety of specific markers were used to identify their fate. Some ventrally emigrating neural tube cells differentiated into neurons and glial cells, indicating that the enteric nervous system in the foregut develops from an additional source of precursor cells. It was also found that some of these cells differentiated into interstitial cells of Cajal, which mediate impulses between the enteric nervous system and smooth muscle cells, whereas others differentiated into epithelium. Altogether, these results indicate that the ventrally emigrating neural tube cells are multipotential. More importantly, they reveal a novel source of precursor cells for the neurons and glial cells of the enteric nervous system. The developmental and functional significance of the heterogeneous origin of the cell types remains to be established.

It is generally believed that after the emigration of neural crest, the neuroepithelial cells of the neural tube are committed to differentiate only as neurons and supporting cells of the central nervous system. Neural crest cells arise from the dorsal portion of the developing neural tube and contribute to the formation of the peripheral nervous system and a variety of non-neural structures. In contrast to this view we have recently shown, by focal application of the vital dye Dil in duck embryos, that an additional population of cells emigrates from the neural tube. By using an entirely different technique we confirm and extend these observations in the chick embryo. Replication-deficient retroviral vector LZ12 containing the gene LacZ was utilized to label the neural tube cells. The viral concentrate was microinjected into the lumen of the rostral hind-brain neural tube, considerably after the completion of emigration of neural crest cells. The labeled cells were monitored in whole mounts and histological sections. Initially, the labeled cells were restricted to the neuroepithelium of the hindbrain neural tube. Subsequently, they were seen in the neural tube and in the ganglion of the fifth cranial nerve (trigeminal ganglion). Later, they migrated beyond the trigeminal ganglion, i.e., into the mesenchyme of the first pharyngeal arch. Immunostaining with the neural crest cell marker, HNK-1, indicated that the emigrated neuroepithelial cells were HNK-1 negative. It is concluded that in the chick embryo some neuroepithelial cells emigrate at the site of attachment of the trigeminal nerve, migrate into the ganglion and then into the mesenchyme of the first arch. This cell population differs antigenically from the neural crest cells.