Gross Anatomy and Embryological Development of the Brain, Brainstem, and Cerebellum
Gross Anatomy
Brain (Cerebrum)
The cerebrum consists of two hemispheres connected by the corpus callosum, with a highly folded cortical surface organized into gyri (ridges) and sulci (grooves). The cerebral cortex is arranged in six layers, with early-born neurons occupying deep layers and late-born neurons migrating to superficial layers 1. The cortex contains both excitatory pyramidal neurons (originating from the dorsal telencephalon) and inhibitory interneurons (migrating from the medial and caudal ganglionic eminences) 1.
The internal capsule serves as the major white matter pathway, with three main outlets leading to the epithalamus, dorsal thalamus, and mesencephalon 2. Deep gray matter structures include the basal ganglia and thalamus.
Brainstem
The brainstem is organized into three distinct layers extending its entire length: the basis (anterior), tegmentum (middle), and tectum (posterior) 3, 4.
The brainstem divides caudo-rostrally into:
- Medulla oblongata (myelencephalon) - contains the pyramidal decussation
- Pons (metencephalon) - shows volume expansion in human evolution
- Mesencephalon (midbrain) - contains superior and inferior colliculi in the tectum
Motor pathways descend through the basis, while cranial nerve nuclei (CN III-XII) are arranged mediolaterally in the tegmentum based on function: somatic motor (medial), visceral motor, visceral sensory, and somatic sensory (lateral) 3, 4. The tegmental reticular formation forms the brainstem core with a lattice structure providing maximum convergence and divergence of information 4.
Cerebellum
The cerebellum consists of a midline vermis and two lateral hemispheres with a highly folded cortical surface. The cerebellar cortex contains radially and tangentially arranged cells, with the external germinal layer formed by tangentially-oriented cells 2. Deep cerebellar nuclei include the dentate nucleus, connected via superior and inferior cerebellar peduncles 2.
Embryological Development
Timeline of Brain Development
Neuronal proliferation in the dorsal telencephalon begins at 5-6 gestational weeks, decreases after 16 weeks, and finishes around 22-25 gestational weeks 1.
Stage 1: Cell Proliferation and Apoptosis (5-25 weeks)
Pyramidal neuronal and glial precursors are generated from neuroepithelial cells in the ventricular zone (VZ) adjacent to the lateral ventricle 1. The developmental sequence proceeds as follows:
Neuroepithelial cells divide symmetrically and undergo interkinetic nuclear migration, forming a pseudostratified monolayer 1
Neuroepithelial cells convert to apical radial glial cells (aRGC), which divide either symmetrically (producing two progenitors) or asymmetrically (generating a progenitor and a neuron, directly or via intermediate progenitors) 1
Intermediate progenitors divide in the subventricular zone (SVZ) before generating neurons 1
The outer SVZ expands basally and contains outer radial glia cells (oRGC), which are crucial for cortical expansion and gyrification in humans 1
Disruptions at this stage cause microcephaly (reduced proliferation/increased apoptosis) or megalencephaly (enhanced proliferation/reduced apoptosis) 1.
Stage 2: Neuronal Migration
Migration begins when the first neurons are formed, with aRGC spanning from ependyma to pia, functioning as a stable radial scaffold for neuronal migration 1. Cortical inhibitory interneurons are generated separately in the medial and caudal ganglionic eminences and undertake different migration trajectories to the dorsal telencephalon 1.
Disruptions cause heterotopias (neurons in abnormal locations), lissencephaly spectrum disorders (agyria, pachygyria, subcortical band heterotopia), or cobblestone malformations 5, 1.
Stage 3: Post-Migrational Development
This stage involves cortical organization, with temporal patterning determining laminar identity. Disruptions result in polymicrogyria or focal cortical dysplasia 1.
Brainstem and Cerebellar Development
The brainstem has an ectodermal origin and is composed of four parts: diencephalon, mesencephalon, pons, and medulla oblongata 3.
The cerebellum initially appears as a plate with an enlarged internal bulge, possessing radially and tangentially arranged cells forming the external germinal layer 2. The dentate nucleus, inferior and superior cerebellar peduncles, and cerebellar commissures are present by stage 23 (eighth embryonic week) 2.
There is heterochrony between supratentorial (forebrain) and infratentorial (brainstem and cerebellum) growth, with an inversion of the infra- to supratentorial ratio after 30 weeks gestation 6, 7. The brainstem grows rapidly before 30 weeks and slowly afterward, while the cerebellum exhibits slow growth before 30 weeks and accelerated growth after 30 weeks 6.
Critical Developmental Milestones
- Stage 21 (eighth week): Cortical plate appears in the future insular area 2
- Stage 22: Internal capsule outlets develop; lateral olfactory tract is well-developed 2
- Stage 23: Anterior commissure appears; superior and inferior colliculi distinguishable; pyramidal decussation present 2
- 30 weeks gestation: Critical turning point in brainstem and cerebellar growth patterns 6
Developmental Relationships
The growth of brainstem and cerebellum is closely related to the cerebral cortex, especially the posterior frontal lobe, parietal lobe, and occipital cortex, with stronger relationships to the right hemisphere than the left 6.
Human telencephalic evolution manifests in volume increases of cerebral crura, pons, cerebellar hemispheres, olives, pyramidal tract, and medial lemniscus, though spatial constraints of the posterior fossa limited proportional brainstem expansion 4.