24th November 2023

Embryology

The period of brain development least well informed by human neuroimaging is the embryological period – that is, the first 8 weeks following conception. Instead, much of what is known about brain maturation during this time comes from rodent and non-human primate histology (and relatively few post-mortem human studies).

During weeks 1 and 2 of development, the fertilised egg divides repeatedly to become the morula (a solid 16- to 32-celled mass) and then the blastocyst (a fluid-filled 50- to 150-celled mass), which subsequently embeds within the uterine wall. During week 3, the two-layered embryo becomes a three-layered structure through the process of gastrulation. Gastrulation gives rise to different stem cell lines, such as neural stem cells – so-called neural progenitor cells – arranged as the neural plate.

Neurulation

During days 20–27, the outer ridges of the neural plate fold inwards and fuse to form the hollow neural tube in a process termed neurulation. Meanwhile, the release of molecular signals from elsewhere in the embryo encourages the rostral–caudal (head-to-toe) organisation of this primitive nervous system. Neural tube closure begins medially and extends axially, with the rostral (anterior) and caudal (posterior) neuropores closing on days 25 and 27, respectively.

Just prior to closure, however, the rostral end of the neural tube forms 3 brain vesicles: the prosencephalon, the rhombencephalon and the mesencephalon. The prosencephalon further divides to form the telencephalon and diencephalon, which give rise to the forebrain; the rhombencephalon splits into metencephalon and myelencephalon, which later become hindbrain; and the mesencephalon becomes the midbrain (without subdivision). This process is completed during week 7.

From days 25 to 42, rapid, symmetrical division of neural progenitor cells significantly increases their number. Thereafter, asymmetrical division gradually increases the number of new neuronal cells relative to neural progenitor cells. Cell division occurs in ‘proliferative zones’ such as the ventricular zone and subventricular zone (so-called due to their anatomical proximity to the embryological origins of the lateral ventricles).