The Timing and Sequence of Appearance of Neuromeres and Their Derivatives in Staged Human Embryos

Abstract

Serial sections of 215 human embryos from Carnegie stages 6-17 were investigated, and 85 graphic reconstructions were prepared. It is proposed that neuromeres be defined as morphologically identifiable transverse subdivisions perpendicular to the longitudinal axis of the embryonic brain and extending onto both sides of the body. It is proposed further that primary neuromeres be redefined as the early-appearing larger divisions of the open neural folds, and secondary neuromeres as the smaller subdivisions that are found both before and after closure of the neural tube. In the light of these definitions, 6 primary neuromeres can be detected in the human brain at stage 9, and a maximum of 16 secondary neuromeres at stage 14. The relationships of the 8 rhombomeres to the associated neural crest, as well as to the pharyngeal arches and the exits of the cranial nerves, are tabulated. Rhombomere 8 (Rh. 8) is intermediate between the more rostral neuromeres and the spinal cord, and its neural relationships indicate that the four occipital somitic pairs do not impress a strictly repetitive pattern as in the spinal cord. Hence, it is suggested that Rh. 8 depends on both intrinsic and extrinsic factors. The synencephalon, parencephalon, and isthmic neuromere can be distinguished in stage 13. In stage 14, rostral and caudal portions of the parencephalon are recognizable, and the full complement of 16 neuromeres is now present. The medial ventricular eminence appears in the diencephalon (D1). A longitudinal organisation begins to be superimposed on the neuromeres, as now indicated by the appearance of the hypothalamic cell cord. This continues in stage 15, when the hypothalamic sulcus develops. That groove, however, is not continuous with the sulcus limitans. In the diencephalon, five longitudinal zones can be discerned. In stage 16, fibre tracts, such as the habenulo-interpeduncular (fasciculus retroflexus) and the tract of the posterior commissure, outline the boundaries of the synencephalon. In stage 17, the tract of the zona limitans intrathalamica (along the marginal ridge in the parencephalon) is an important landmark. This is the last stage in which all the neuromeres can be distinguished. The supramamillary recess becomes defined and is the termination of the sulcus limitans: the alar/basal distinction is inappropriate in the human forebrain. The number and identity of the neuromeres in the human brain, their precise sequence of appearance, and the stages at which they appear are here clarified for the first time. The results of various studies of domains of gene expression indicate that, although in some instances such territories follow the morphological neuromeres, in others they may cross interneuromeric boundaries. It is concluded that the precise morphological study of neuromeres in any given species is necessary for correlative investigations of gene expression.