Prenatal development of the human nucleus ambiguus during the embryonic and early fetal periods

Abstract

The ontogenetic development of the nucleus ambiguus was studied in a series of human embryos and fetuses ranging from 3 to 12.5 weeks of menstrual age (4 to 66 mm crown-rump length). They were prepared by Nissl and silver methods. Nucleus ambiguus neuroblasts, whose neurites extend towards and into the IXth and rostral Xth nerve roots, appear in the medial motor column of 4-6-week-old embryos (4.25-11 mm). These cells then migrate laterally (6.5 weeks, 14 mm) to a position near the dorsal motor nucleus of X. At 7 weeks (15 mm), nucleus ambiguus cells begin their migration, which progresses rostrocaudally, into their definitive ventrolateral position. The basic pattern of organization of the nucleus is established in its rostral region at 8 weeks (22.2-24 mm) and extends into its caudal region by 9 weeks (32 mm), when its nearly adult organization is evident. Cells having the characteristics of mature neurons first appear rostrally in the nucleus during the 8.5-9-week period (24.5-32 mm), gradually increase in number, and constitute the entire nucleus at 12.5 weeks (65.5 mm). Definitive neuronal subgroups first appear at 10 weeks (37.5 mm) in the large rostral nuclear region. These features suggest that the human nucleus ambiguus develops along a rostrocaudal temporospatial gradient. Evidence indicates that function of nucleus ambiguus neurons, manifested by fetal reflex swallowing, occurs after the cells migrate into their definitive position, establish the definitive nuclear pattern, and exhibit mature characteristics.

Cytoarchitecture and musculotopic organization of the facial motor nucleus in Cebus apella monkey

“…On the other hand, our results support the hypothesis raised for humans by Jacobs (1970) and Brown (1990) that those neuroblasts that first complete their differentiation and cease migration are the first to become functional. The migration of facial neuroblasts in the midline neuroepithelium occurs along a diagonal axis from the rostral dorsomedial to the caudal ventrolateral position (Jacobs, 1970;Auclair et al 1996;Swanson et al 1999).…”

Naturally occurring motoneuron cell death in rat upper respiratory tract motor nuclei: A histological, fast dil and immunocytochemical study in the nucleus ambiguus

“…As such, these results indicate organization of a distinct nucleus between El5 and E17, and maturation and further differentiation of the neuroblasts through E19. This overall temporospatial pattern observed in the rat NA (i.e., initial appearance of NA rostrally followed by organization throughout the caudal extent followed by maturation of motoneurons) has also been noted in a histological study of the developing human NA (Brown, 1990). Furthermore, our observed maturation of motoneurons in NA coincides with critical periods in the development of rat muscle fibers (Rubinstein and Kelly, 1981) and, as such, provides a temporal basis for coordinated developmental sequences between motoneurons and their target muscles (Ross et al, 1987).…”

“…Labeling of migrating motoneurons was considered possible based on three observations: (1) Motor axons in the mature NA initially project dorsally before ''looping'' ventrolaterally to leave the brainstem, thus implying migration after axogenesis (Kalia and Mesulam. 1980;GrClot et al, 1989); (2) histological studies of developing neuroblasts, including those in NA, observed axonal projections leaving the central nervous system prior to and during the period of migration (Levi- Montalcini, 1964;Heaton et al, 1978;Brown, 1990); and (3) neural tracing studies have previously been shown to label apparently migrating neurons (Heaton and Moody, 1980;Lumsden and Keynes, 1989). These findings suggested that application of tracer to URT nerves, just distal to their exit from the brainstem, would label any motoneurons still migrating to the ventrolateral NA during the period of MCD.…”

Establishment of vagal sensorimotor circuits during fetal development in rats

“…The target of early NA axons is likely the esophagus because the NA innervates the esophagus but not the stomach or other abdominal viscera in mature rats (Bieger and Hopkins, 1987;Rinaman and Miselis, 1987;Altschuler, Bao, and Miselis, 199 1;Altschuler, Ferenci, Lynn, and Miselis, 199 1 ) . An early lateral migration of NA motor neurons has also been described in human fetuses (Brown, 1990) and appears to be a developmental characteristic of motor nuclei that supply branchiomeric muscles (Heaton and Moody, 1980), such as those within the esophagus. These NA motor neurons may already receive central synaptic inputs at E13, as motor neuron dendritic growth has been shown to occur synchronously with the formation of axodendritic synapses (Vaughn et a]., 1974).…”

“…As in the adult, most NA axons arch dorsally and then turn ventrolaterally to join the heavily labeled bundle of exiting DMV motor axons. This axonal arching pattern indicates that NA motor neurons first migrate radially, sending their axons out of the same region of the ventrolateral medulla where DMV axons exit, but then the NA somata subsequently migrate ventromedially (see also Brown, 1990).…”