Ontogeny of the human central nervous system: What is happening when?
Introduction
The development of the central nervous system (CNS) is a complex and long-lasting process—this can be read in many textbook chapters (e.g., [1], [2]). The aim of the present review is to assess as accurately as possible when specific events take place during ontogeny of the human nervous system. Knowledge on the exact timing of ontogenetic events during human brain development will shed light on the mechanisms playing a role in the determination of sequelae after adversities occurring at a specific point in time during brain development (excellently reviewed in Ref. [1]). Knowledge on the timing of developmental processes in the human nervous system is also pertinent for the development of appropriate neurological assessment techniques and for the interpretation of neurological findings at early age. It might also facilitate our understanding of the timing of intervention in infants at high risk for or with developmental disorders. For the timing of early intervention it is generally assumed that ‘earlier is better’ [3], but a recent review on the effect of early intervention in ‘high-risk’ infants indicated that this is not necessarily the case [4].
In the present review, we based ourselves predominantly on human data. For the missing links, we preferably used non-human primate data; when such data were not available, rodent data were used. We zoomed in on ontogenetic events in the telencephalon, i.e., the major neural determinant of human behaviour. In order to facilitate the understanding of the timing of the various events we included a schematic timetable of the various developmental processes (Fig. 1).
Section snippets
Cell proliferation and neuronal migration
In the fifth week postmenstrual age (PMA), the neural tube starts to develop. Neural tissue differentiates along several axes: (a) a longitudinal axis, where the major subdivisions of the central nervous system (CNS), namely the forebrain, midbrain and spinal cord, develop; (b) a vertical axis that establishes dorsal and ventral sides; and (c) a horizontal axis that establishes medial and lateral structural growth. The axes of the neural tube are associated with gradients of genetic expression
Possible clinical consequences of the neural ontogenetic timetable
From our summarizing (Fig. 1), it is clear that major part of the structural development of the telencephalon occurs during early life. But the figure also indicates that it takes about two decades before the central nervous system obtains a more or less adult configuration.
The continuous neurobiological changes during pre- and postnatal life have important clinical consequences. First, the fact that a child has an age-specific nervous system invokes the need of an age-specific neurological
Concluding remarks
The development of the human central nervous system is characterized by a protracted, neatly orchestrated chain of specific ontogenetic events. The continuous changes of the nervous system have consequences for vulnerability to adverse conditions, for diagnostics and for physiotherapeutical intervention. Our review suggests that intervention prior to 40–44 weeks PMA rather should be restricted to forms of intervention which aim at mimicking the intrauterine environment, such as NIDCAP. After
Acknowledgements
We thank Drs. C.H. Blauw-Hospers, Drs. H. Bouwstra, Prof. Dr. O. F. Brouwer, Drs. K.R. Heineman and Dr. C.N. van der Veere for their valuable remarks on a previous draft of this manuscript. The study was supported by the Johanna KinderFonds, Stichting Fonds de Gavere and the Post-graduate School BCN Groningen.
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