Neural Development Study Notes

Neural Development

Overview of Key Stages

  • Fertilization to Gastrulation

  • Neural Plate Formation ~ PD 20

  • Neural Tube Closing (PD 21 – PD 26)

  • Molecular Signals

  • Development of Brain Subdivisions (PD 21 – Birth)

  • Cell Proliferation

  • Cell Migration

Timeline and Stages of Development

  • Fertilization

    • Day 0: Oocyte (egg) fertilized by sperm cell to form zygote.

  • Day 1: Zygote undergoes first cleavage, resulting in a two-cell stage.

  • Day 2: Formation of four-cell stage from two-cell stage.

  • Day 3: Continued cleavage results in eight-cell stage.

  • Day 4: Morula stage reached as more cell divisions occur.

  • Day 5: Formation of blastocyst, important structure for implantation.

Morphological Stages

  • 2-cell stage to 32-cell stage before implantation, leading to:

    • Trophoblast (outer layer)

    • Embryoblast (inner cell mass)

    • Blastocyst becomes implanted into the uterine wall.

Gastrulation (Around PD 14)

  • Formation of three-layered structure (ectoderm, mesoderm, endoderm).

    • Epiblast: The layer that contributes to the embryo.

    • Hypoblast: Extra-embryonic structures.

  • Primitive Streak: Structure that develops to establish body axes.

  • Layers Derived During Gastrulation:

    • Ectoderm: Will become skin and nervous system.

    • Mesoderm: Will develop into muscles, skeleton, and other organs.

    • Endoderm: Will form the lining of the gut and associated organs.

Neural Development Phases

  • Neural Plate Formation

    • Signals from the notochord induce thickening of the central ectoderm to form the neural plate (neural ectoderm).

    • Importance of BMP (Bone Morphogenic Proteins) inhibition for proper development of the neural plate.

    • BMP must be turned OFF to prevent cells from becoming skin cells.

    • BMP inhibitors secreted by the primitive node and streak include:

      • Noggin

      • Chordin

Neurulation Process

  • Begins with the inward sinking of the neural plate:

    • Neural Crests: Form from ectoderm on either side of the neural plate.

    • Neural Tube Formation: Neural crests fuse to form the neural tube which will become the CNS (Central Nervous System).

    • Changes in Gene Transcription: Notochord secretes chemicals that direct cytoskeletal changes in neural plate cells.

Stages of Neurulation

  • Day 17 to Day 23: Formation of the neural groove and subsequent folding of the neural tube with key structures indicated, such as the:

    • Neural fold

    • Neural crest cells

    • Somites (originally segmented mesoderm).

Closure of the Neural Tube

  • Occurs between Day 24-26 with anterior and posterior neuropores closing.

  • Importance of closure: Failure of closure leads to conditions such as Spina Bifida, where the spinal cord is exposed.

Molecular Signals and Cell Fate

  • Signaling Molecules influencing development include:

    • Retinoic Acid (from Vitamin A)

    • Fibroblast Growth Factors (FGFs)

    • Transforming Growth Factor (TGF)

    • BMPs

    • Sonic Hedgehog (Shh)

    • Wnt family of proteins.

  • Altering these signals can lead to teratogenic effects, such as the introduction of Accutane (13-cis-retinoic acid), which has led to miscarriages and developmental defects.

Development of Brain Subdivisions (PD 21 – Birth)

  • Key Structures Formed:

    • Forebrain (Prosencephalon)

    • Telencephalon: Cerebrum

    • Diencephalon: Thalamus, Hypothalamus

    • Midbrain (Mesencephalon): Forms part of the brainstem.

    • Hindbrain (Rhombencephalon):

    • Metencephalon: Pons, Cerebellum

    • Myelencephalon: Medulla Oblongata

  • Each region of the embryonic brain gives rise to adult structures.

    • E.g., Third ventricle arises from diencephalon.

Cell Proliferation

  • Cell Proliferation Phase begins around 60 days.

  • In humans, approximately 250,000 new neurons are generated each minute during peak proliferation.

Cell Cycle and Mitosis

  • Stages of the Cell Cycle:

    1. Interphase

    • Gap 1 (G1): Cell growth.

    • S Phase: DNA replication.

    • Gap 2 (G2): Preparing for division.

    1. Mitotic Phase:

    • Prophase: Chromatin condenses, nuclear membrane dissolves.

    • Metaphase: Chromosomes align at the equatorial plane.

    • Anaphase: Sister chromatids separated to opposite poles.

    • Telophase: Chromosomes decondense, nuclear membranes reform.

  • Cytokinesis: Splitting of the cytoplasm to complete cell division.

Cell Division Types

  • Symmetric Division: Two identical stem cells that remain in the cycle.

  • Asymmetric Division: One stem cell and one differentiated cell (e.g., neuroblast).

Cell Migration Mechanisms

  • Neurons migrate along radial glia scaffolds from deeper to superficial cortical layers.

  • Types of Cell Migration:

    • Radial migration: Movement along radial glial cells.

    • Non-radial migration: More complex pathways that differ in timing and patterns.

Disorders of Neuronal Migration

  • Various disruptions in cell migration can lead to disorders:

    • Lissencephaly: Characterized by a smooth brain surface due to lack of folds.

    • Polymicrogyria: Numerous small gyri with a thick cortex.

    • Agenesis of the Corpus Callosum: Absence of this structure leading to various cognitive and physical issues.

Conclusion and Learning Outcomes

  • Describe the stages from fertilization to blastocyst development.

  • Explain gastrulation and its cellular layers.

  • Discuss neurulation and potential consequences of neural tube defects.

  • Identify the molecular signals guiding cell fate decisions.

  • Define teratogens, specifically the role of retinoic acid.

  • Detail the formation and fates of neural crest cells.

  • Summarize brain subdivisions and the major adult structures derived from them.

  • Understand the cell cycle and differential roles of symmetric vs. asymmetric division.

  • Elaborate on neuronal migration processes and their disorders.