The development of the neural crest in the human

The first systematic account of the neural crest in the human has been prepared after an investigation of 185 serially sectioned staged embryos, aided by graphic reconstructions. As many as fourteen named topographical subdivisions of the crest were identified and eight of them give origin to ganglia (Table 2). Significant findings in the human include the following. (1) An indication of mesencephalic neural crest is discernible already at stage 9, and trigeminal, facial, and postotic components can be detected at stage 10. (2) Crest was not observed at the level of diencephalon 2. Although pre-otic crest from the neural folds is at first continuous (stage 10), crest-free zones are soon observable (stage 11) in Rh.1, 3, and 5. (3) Emigration of cranial neural crest from the neural folds at the neurosomatic junction begins before closure of the rostral neuropore, and later crest cells do not accumulate above the neural tube. (4) The trigeminal, facial, glossopharyngeal and vagal ganglia, which develop from crest that emigrates before the neural folds have fused, continue to receive contributions from the roof plate of the neural tube after fusion of the folds. (5) The nasal crest and the terminalis-vomeronasal complex are the last components of the cranial crest to appear (at stage 13) and they persist longer. (6) The optic, mesencephalic, isthmic, accessory, and hypoglossal crest do not form ganglia. Cervical ganglion 1 is separated early from the neural crest and is not a Froriep ganglion. (7) The cranial ganglia derived from neural crest show a specific relationship to individual neuromeres, and rhombomeres are better landmarks than the otic primordium, which descends during stages 9–14. (8) Epipharyngeal placodes of the pharyngeal arches contribute to cranial ganglia, although that of arch 1 is not typical. (9) The neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there rostrad to the truncus arteriosus at stage 12 is identified here, for the first time in the human, as the cardiac crest. (10) The hypoglossal crest provides cells that accompany those of myotomes 1–4 and form the hypoglossal cell cord at stages 13 and 14. (11) The occipital crest, which is related to somites 1–4 in the human, differs from the spinal mainly in that it does not develop ganglia. (12) The occipital and spinal portions of the crest migrate dorsoventrad and appear to traverse the sclerotomes before the differentiation into loose and dense zones in the latter. (13) Embryonic examples of synophthalmia and anencephaly are cited to emphasize the role of the neural crest in the development of cranial ganglia and the skull. Table 2 The origin and nomenclature of the components of the neural crest in the human, including their relationship to the neuromeres and their initial appearance, as well as the arrival of ganglia, related to somitic number and developmental stages Keywords: cardiac crest, cranial and spinal ganglia, epipharyngeal placodes, human embryo, hypoglossal crest Introduction What is now termed the neural crest was identified first in 1868 in the chick embryo by Wilhelm His, Senior, who designated it as Zwischenstrang, literally an ‘intermediate cord’ (His, 1868). It was detected independently in selachians a decade later by Balfour. The term neural crest (crista neuralis), appropriate particularly for a transient dorsal ridge on the neural tube in amphibians, received official recognition in the Nomina embryologica (1967, 1977). In German it is called Neuralleiste. Much of the pioneer work on neural crest was in amphibians, and is associated historically with the name Horstadius, whereas subsequent studies on derivatives of the crest have been undertaken particularly in avian embryos and are associated especially with LeDouarin and her group. The mammalian neural crest (reviewed by Morriss-Kay et al. 1993) is now being investigated by labelling of crest cells either by WGA or by DiI (e.g. Fukiishi & Morriss-Kay, 1992; Serbedzija et al. 1992). More recently crest cells have been identified in transgenic mice, providing valuable information on the developing heart (Jiang et al. 2000), the face and teeth (Chai et al. 2000), and the vault of the skull (Jiang et al. 2002) as well as the neck and shoulder (Matsuoka et al. 2005). The neural crest is characterized by a wide variety of derivatives, including notably spinal and cranial ganglia, as found by His. The origin, migration, and fate of the cells of the crest have been studied extensively in a variety of species. Furthermore, it is generally thought that the evolution of the neural crest was instrumental in that of vertebrates. Cells of the neural crest are generally distinguishable by being relatively larger and more rounded than their neighbours, and they may occur in groups or form strands. There are distinct differences between the neural crest cells and the surrounding mesenchyme (Morriss-Kay et al. 1993), except in the transitional zone between the two groups (Baxter & Boyd, 1939). Consequently it has been possible to identify a number of components of the crest in the human by regular microscopy. A particularly striking example is provided by the emigrating crest cells at stage 12 (Fig. 4A), which give a ‘frightened hedgehog’ appearance to the optic vesicles (Bartelmez & Blount, 1954, Fig. 17). An important technical step (frequently omitted, however) is the construction of precise three-dimensional reconstructions. Fig. 4 The neural crest at stage 12. The planes of sections of A, C, and D are shown in the key. Alum cochineal/haematoxylin and eosin. (A) Optic crest is clearly emigrating from the optic vesicle. (B) Spinal crest in the thoracic region. The roof cells of the ... Although considerable information can be obtained in the human concerning the origin of crest cells, only the very early migratory pathways can be detected in standard morphological examinations. Nevertheless, migration has been clarified in several regions, e.g. the hypoglossal cord (O’Rahilly & Muller, 1984) and the nasal crest (Muller & O’Rahilly, 2004). It would be difficult to find a structure in the human that has not been studied systematically. Surprisingly the neural crest is such and the current investigation was undertaken to fill an important lacuna in the literature on human embryology. The main objectives were: (1) to provide a systematic account of the neural crest in the human embryo using standard histological techniques, including silver, and precise three-dimensional graphic reconstructions; (2) to search as far as possible for indications of the origin, early migratory pathways, and derivatives of the neural crest in the human material available; (3) to reassess the relationships of the neuromeres, the epipharyngeal placodes, and the pharyngeal arches to the neural crest in the human; (4) to present all data in terms of the established staging system; and (5) to indicate any noteworthy differences between the human findings and those reported in other mammals.