Development of the CNS II

Development of the Central Nervous System (Part II) - Brain Development

Objectives

  • Understand the formation of different brain vesicles.

  • Understand the development of myelencephalon (medulla oblongata) and metencephalon (pons and cerebellum).

  • Understand the development of the midbrain.

  • Understand the development of diencephalon and telencephalon.

  • Study cranial defects including cranium bifida, hydrocephalus, and microcephaly.

Formation of Brain Vesicles

  • Neural Tube: Early embryonic structure that later develops into the central nervous system.

  • Primary Brain Vesicles: The primary divisions of the brain that arise from the neural tube.

    • Prosencephalon (Forebrain):

    • Develops into the Telencephalon and Diencephalon.

      • Telencephalon: Forms cerebral hemispheres, including cortex, white matter, and basal nuclei.

      • Diencephalon: Forms structures such as the thalamus, hypothalamus, and epithalamus, with the third ventricle as the associated cavity.

    • Mesencephalon (Midbrain): Develops into the midbrain and retains the same name.

    • Rhombencephalon (Hindbrain): Further divides into the Metencephalon and Myelencephalon.

    • Metencephalon: Forms the pons and cerebellum, with the fourth ventricle as the associated cavity.

    • Myelencephalon: Forms the medulla oblongata and contributes to the central canal structure of the spinal cord.

Frontal (Coronal) Section of the Brain

  • Illustrates major divisions:

    • Cerebrum (Telencephalon)

    • Thalamus (Diencephalon)

    • Midbrain (Mesencephalon)

    • Pons (Metencephalon)

    • Medulla (Myelencephalon)

    • Spinal Cord

Folding of the Brain

  • Midbrain Flexure: Occurs at the end of the fifth week of gestation. The forebrain folds ventrally and posteriorly around the midbrain. It is also referred to as the cephalic flexure.

  • Cervical Flexure: A ventral flexion occurs between the hindbrain and spinal cord from the 4th to the 8th week of development.

  • Pontine Flexure: Dorsal flexion at the hindbrain that divides it into metencephalon and myelencephalon. This occurs between the 5th and 8th weeks.

Derivatives of Hindbrain (Rhombencephalon)

  • Involves the hindbrain's characteristics and structures:

    • Metencephalon: Pons and cerebellum.

    • Myelencephalon: Medulla oblongata.

Development of Myelencephalon (I)

  • Divergence of lateral walls of the neural tube, causing:

    • Alar plates lie lateral to basal plates.

    • Alar plates neuroblasts develop into sensory nuclei (afferent).

    • Basal plates neuroblasts form efferent motor nuclei.

    • Rostral part has olivary nuclei from alar plates neuroblasts.

    • Caudal part contains

    • Gracile nuclei (medial)

    • Cuneate nuclei (lateral)

    • Pyramids (fiber bundles in the ventral area).

Development of Myelencephalon (II)

  • Lateral wall divergence leads to stretching and thinning of the ependymal roof, forming:

    • The lower part of the 4th ventricle.

    • Tela choroidea invaginates into the 4th ventricle and differentiates into the choroid plexus, producing cerebrospinal fluid (CSF).

    • Vascular pia mater combines with the ependymal roof to form the tela choroidea.

Functional Classification of Nerve Fibers

  • Types of Nerve Fibers:

    • General Somatic Afferent (GSA): General sensation from somatic structures (skin, muscles, joints) regarding pain, temperature, touch, pressure, proprioception.

    • Special Somatic Afferent (SSA): Senses from somatic structures (vision, hearing, balance).

    • General Visceral Afferent (GVA): Sensation from visceral organs (stretch, pain, hunger).

    • Special Visceral Afferent (SVA): Taste and smell from visceral structures.

    • Efferent Fibers: Coarse into voluntary and involuntary motor fibers.

Development of Myelencephalon (III)

  • Basal Plate Neuroblasts gives rise to the following motor nuclei:

    • Medial Somatic Efferent Group: Neurons of the hypoglossal nerve (XII).

    • Intermediate Special Visceral Efferent Group: Neurons of vagus (X) and glossopharyngeal (IX) nerves, innervating pharyngeal arch muscle.

    • Lateral General Visceral Efferent Group: Neurons supplying involuntary muscle in respiratory and gastrointestinal tracts.

Development of Myelencephalon (IV)

  • Alar plate contains three sensory relay nuclei groups:

    • Somatic Afferent Group: Receives general sensations (touch, temperature, pain) from head/neck and nasal/oral cavities (IX).

    • Special Somatic Afferent: Auditory and balance signals from vestibulocochlear (VIII).

    • General Visceral Afferent Group: Receives impulses from the heart and gastrointestinal tract via the vagus nerve (X).

    • Special Visceral Afferent Group: Impulses received from taste buds (IX).

Development of Metencephalon (I)

  • Neural lumen forms the upper part of the 4th ventricle.

  • Alar plate specializes into the cerebellum, while basal plates develop motor nuclei.

  • Some alar plate neuroblasts migrate to form pontine nuclei on the ventral side.

Organization of Alar and Basal Plate Neurons in Metencephalon

  • Basal Plate Neurons:

    1. Medial Somatic Efferent Group: Neurons of abducens nerve (VI).

    2. Special Visceral Efferent Group: Neurons of trigeminal (V) and facial nerves (VII).

    3. General Visceral Efferent Group: Neurons supplying submandibular glands.

  • Alar Plate Neurons:

    1. Special Somatic Afferent Group: Vestibulocochlear nerve (VIII).

    2. General Somatic Afferent Group: Trigeminal nerve (V).

    3. Special Visceral Afferent Group: Facial nerve (VII).

    4. General Visceral Afferent Group: Facial nerve (VII).

Development of Metencephalon (II)

  • Cerebellum:

    • Begins to develop at the end of the 6th week and continues to grow postnatally.

    • Cerebellar swellings enlarge and fuse in the median plane.

  • Pons:

    • Ventral region contains nerve fibers connecting cerebrum, cerebellum, and spinal cord, forming a bulky ridge on its anterior aspects.

External Features of Cerebellum

  • Comprised of:

    • Two cerebellar hemispheres and a median vermis.

    • Superior and inferior surfaces.

    • Three fissures: Primary, Horizontal, Posterolateral.

    • Three lobes in each hemisphere: Anterior, Posterior, Flocculonodular.

Development of Midbrain

  • Neural lumen narrows to form the cerebral aqueduct connecting the 3rd and 4th ventricles.

  • Sensory neuroblasts migrate to form superior and inferior colliculi, relating to visual and auditory reflexes, respectively.

  • The marginal layer forms cerebral peduncles, with nerve fibers traveling between the cerebrum and spinal cord.

Derivatives of the Forebrain (Prosencephalon)

  • Structures include:

    • Telencephalon: Forms the cerebrum.

    • Diencephalon: Comprises the epithalamus, thalamus, and hypothalamus.

Development of Diencephalon

  • Walls formed by alar plates:

    • Epithalamus: Develops from the alar and roof plate.

    • Thalamus: Develops from the alar plate.

    • Hypothalamus: Arises from both alar and floor plates beneath the hypothalamic sulcus, forming the 3rd ventricle as a cavity.

Development of Telencephalon (I)

  • Composed of:

    • Median part and two lateral telencephalic vesicles.

    • Lateral vesicles expand to develop into cerebral hemispheres.

    • Separation occurs by a connective tissue septum (falx cerebri).

    • Initial smooth surface transforms with growth into gyri (convolutions) and sulci (grooves).

Development of Telencephalon (II)

  • As cerebral hemispheres expand, they cover the diencephalon and midbrain.

  • Develop into frontal, parietal, occipital, and temporal lobes with massive folding observed in the temporal lobes.

  • Final stages of expansion conceal an area known as the insula.

Cytodifferentiation of the Cerebral Cortex (III)

  1. Initial neuroectoderm formed in ventricular zone, intermediate zone, and marginal zone.

  2. Neuroblasts migrate from ventricular and intermediate to create the cortical plate (CP).

  3. Subventricular zone formed by neuroblasts from the ventricular zone.

  4. Neuroblasts migrate to create the subplate zone.

  5. Together, the cortical plate and subplate become the cerebral neocortex.

  6. Intermediate zone evolves into white matter.

  7. Marginal zone transforms into the molecular layer of the cerebral cortex.

  8. The cerebral cortex bifurcates into:

    • Neocortex (90% of cortical mantle).

    • Allocortex (10% of cortical mantle).

Development of Telencephalon (IV)

  • Corpus Striatum:

    • Expands posteriorly into caudate nucleus (dorsomedial) and lentiform nucleus (ventral lateral).

    • Axons transit through internal capsule to and from the cortex.

    • Is first recognized as swelling in week 5 of development.

Commissures: Interconnecting Fibers

  • Commissures connect cerebral hemispheres across the midline:

    • Anterior Commissure: First to appear, connecting olfactory structures.

    • Hippocampal Commissure: Links the two hippocampi.

    • Corpus Callosum: Largest commissure, developing between weeks 12 and 22, interlinking homologous areas of the cortex.

Ventricular System in the Brain

  • Central canal expands forming ventricles linked by thinner channels:

    • Choroid plexuses secrete cerebrospinal fluid (CSF).

    • CSF pressure is crucial for brain growth.

    • The choroid plexus originates from roof plates of the rhombencephalon and diencephalon and the choroid fissure of the telencephalon.

Neural Tube Defects in the Brain

  • Meningoencephalocele: Herniation of brain tissue and meninges, associated with elevated alpha-fetoprotein (AFP).

  • Meningohydroencephalocele: Herneation includes meninges, brain and ventricular systems (AFP elevation).

  • Cranial Meningocele: Develops due to inadequate neural tube formation, characterized by meninges herniation.

  • Cranium Bifida: A form of neural tube defect.

Microcephaly

  • Conditions leading to microcephaly (small brain) result in small head size.

  • Calvaria growth is dependent on increased pressure from the developing brain.

  • Often leads to mental retardation due to brain underdevelopment.

Hydrocephalus

  • Characterized by thinning brain walls and enlarging skull diameter.

  • Defined by abnormal CSF accumulation in ventricles due to production and absorption imbalance (e.g., caused by choroid plexus adenoma).

References

  • Langman’s Medical Embryology, T.W. Sadler, Lippincott Williams & Wilkins.

  • The Developing Human: Clinically Oriented Embryology, K.L. Moore, T.V.N. Persaud & M.G. Torchia, Saunders.

  • Larsen’s Human Embryology, G.C. Schoenwolf, W. J. Larsen, Churchill Livingstone.