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Neural Tube - Part 2: Morphogenesis and Patterning

Overview of Key Genes and Their Regions

  • Pax7: Expressed in dorsal progenitor domains of the neural tube (dP1-6).

  • Pax6: Higher expression in p0 and p4 progenitor domains.

  • Olig2: Present in PMN (pMN) progenitor regions.

  • Nkx2.2: Expressed in p3 regions of the neural tube.

  • Foxa2: Present at the floor plate (FP).

  • Reference: Le Dréau and Marti, 2012.

Neural Hinge Points

  • Neural hinge points rely on the interplay of signals:

    • BMP (Bone Morphogenetic Protein): Signaling involved in multiple processes.

    • Noggin: Antagonizes BMP signaling.

    • Shh (Sonic Hedgehog): Plays a crucial role in patterning and development of the neural tube.

    • Notochord Signals: Provide essential guidance for adjacent structures.

    • Reference: Gilbert 13.7.

Differential Adhesion During Neural Tube Development

  • Fusion and Separation of Tissues:

    • The fusion of the neural tube and surface ectoderm occurs due to differential adhesion.

    • Expressions:

    • Neural Tube: N-CAM (Neural Cell Adhesion Molecule) and N-cadherin.

    • Surface Ectoderm: E-cadherin.

    • Injection of N-cadherin RNA leads to no separation of the neural tube as both tissue types express similar adhesion molecules, inhibiting fusion.

Role of Differential Adhesion

  • Cell Sorting Mechanism:

    • Cells sort into separate tissues based on their adhesion properties.

    • Visual Representation:

    • Green cells: Very adhesive; sort together in the interior.

    • Red cells: Less adhesive; sort together outside.

    • The sorted organization results from varying degrees of cell adhesion.

Neural Crest Cells

  • Origin and Migration: Neural crest cells originate from the dorsal-most region of the neural tube and migrate to various destinations including:

    • Neurons and glia

    • Chondroblasts

    • Melanocytes and osteoblasts

  • Significance: Contribute to an incredibly diverse range of tissues.

Events in Neural Crest Development

  1. Progressive development of neural tissue:

    • Include figures illustrating vertebrate neural crest development and gene regulatory networks (GRN).

  2. Signaling Modules:

    • Key Signaling Pathways: WNT, BMPs, Notch, FGFs.

    • Neural Crest Specification Modules: Pax3/7, Gbx2, Dlx5/6, FoxD3, and molecular candidates involved in differentiation steps of neural crest cells.

Epithelial to Mesenchymal Transition (EMT)

  • Process Overview: EMT in neural crest cells involves:

    1. Signaling pathways to activate EMT.

    2. Transcription factors determining specificity.

    3. Cadherin switch from E-cadherin to N-cadherin.

    4. Matrix remodeling to enable migration.

    5. Using existing substrates for migration.

Activation of EMT in Cancer

  • Inappropriate Activation: EMT is reactivated in cancer contexts:

    • Transition from epithelial cells to invasive mesenchymal cells.

    • Implications for tumor invasion and metastasis.

Multipotency of Neural Crest Cells

  • Are they multipotent stem cells? Two Hypotheses:

    • Hypothesis 1: Neural crest cells are multipotent stem cells capable of forming diverse cell types.

    • Hypothesis 2: Neural crest cells have limited potential and do not exhibit full multipotency.

  • Fate Mapping Studies: Lineage tracing techniques (Gilbert 15.3) used to understand cell differentiation potential.

Progressive Restriction of Potential

  • As neural crest cells migrate:

    • Their potential becomes progressively restricted, resulting in specific progenitor populations:

    • Cartilage and bone

    • Schwann cells

    • Glia

    • Neurons and melanocytes.

Neurulation Processes

  • Primary Neurulation:

    • Involves the formation of a neural plate from the epithelium, folding to create a neural tube.

    • Key stages include:

    1. Columnarization of neural plate.

    2. Folding and closure processes.

  • Secondary Neurulation:

    • Occurs in the caudal region of the neural tube by mesenchymal cells coalescing to form the medullary cord, which then transitions to epithelium.

    • Key processes include cavitation to form a single lumen from multiple cavities.

Neural Tube Patterning

  • Anatomical Structure: Primary and secondary vesicles developing into various parts of the brain and spinal cord:

    • Forebrain derivatives including:

    • Telencephalon (cerebrum, olfactory lobes).

    • Diencephalon (thalamus).

    • Midbrain and Hindbrain:

    • Metencephalon (cerebellum, pons).

    • Myelencephalon (medulla oblongata).

    • Functional mappings include caloric control, vision, emotion, and reflexes.

Dorsal-Ventral Patterning Mechanisms

  • Morphogen gradients delineating dorsal and ventral identities via:

    • BMP and Wnt Signaling (dorsal) and Shh Signaling (ventral).

Graded Signals and Transcription Factors

  • Graded signals activate various transcription factors in a dorsal-ventral manner that specify the neural fates, impacting cell differentiation and organization.

Next Class: Somitogenesis

  • Overview of the integration between development of the somites and neural structures as part of the overall morphogenetic processes in embryonic development.