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Determination and differentiation

Ganglionic Eminence (GE)

  • Definition: The ganglionic eminence (GE) is a temporary structure in the brain that produces neurons and interneurons.

  • Subdivisions:

    • Lateral Ganglionic Eminence (LGE): Birthplace of interneurons that will populate the neocortex.

    • Medial Ganglionic Eminence (MGE): Gives rise to interneurons migrating to the striatum.

    • Caudal Ganglionic Eminence (CGE): Source of additional interneurons.

  • Other Structures Generated by GE: Neurons populating regions such as the septum, olfactory bulb, and amygdala.

Developmental Timeline

  • Embryonic Day 12: Formation of the GE.

  • Embryonic Day 15.5: Further development related to the neocortex, striatum, and hippocampus.

Nests of DCX+ Cells in Ventral Prenatal Brain

  • Description: A schematic showing a coronal view of the embryonic human forebrain highlighting the medial ganglionic eminence (MGE)

  • **Key Features:

    • DCX+ Cells:

    • Location of nests (designated as DENs) that are involved in the development of the central nervous system.

    • Nestin+ Progenitor Cells:

    • Found in the ventricle zone (VZ) and inner subventricular zone (iSVZ), mixed with outer SVZ (oSVZ).

    • Type I Clusters:

    • Palisades of nestin+ progenitors surrounding DENs.

    • Type II Clusters:

    • Groups of nestin+ progenitor cells in the outer oSVZ.

  • Significance of Proliferation:

    • Indicates multiple progenitor states generating MGE-derived interneurons in the human forebrain.


Chapter 4

Generation of Neural Diversity

  • Neuronal and Glial Diversity: Likely more than 10,000 different types of neurons and glial cells in the human brain, continually being discovered.

  • Comparison Examples:

    • Purkinje cells from guinea pig cerebellum

    • Motoneurons from cat spinal cord

    • Spiny neurons from rat neostriatum

    • Output neurons from cat superior colliculus

Nature vs. Nurture Debate

  • Definition of Terms:

    • Nature: Refers to biological heredity and genetic predispositions inherited at birth, including physical traits and behavioral tendencies.

    • Nurture: Encompasses environmental influences such as parenting style, educational experiences, and cultural background.

  • Interaction of Nurture and Nature: Neurons and glia manifest their identities through both intrinsic cellular decisions and extrinsic environmental cues.

  • Progenitor Cells in Fate Determination:

    • Intrinsically predisposed progenitor cells may receive extrinsic signals that refine their developmental trajectory.

Invariant Lineages and Terminal Selectors

  • Unique Contributions of Cells: Each individual cell contributes distinctly to the overall body form.

  • Transcriptional Hierarchy:

    • Example Illustration:

    • In normal animals, the protein Unc-86 activates Mec-3; their co-expression leads to the formation of a heterodimeric transcription factor that activates specific genes crucial for mechanosensory neuron development.

Extrinsic and Intrinsic Factors Affecting Neural Development

  • Extrinsic Factors:

    • Nutrition

    • Drugs

    • Mental stress

    • Maternal care

    • Neuronal stimulation

  • Intrinsic Factors:

    • DNA methylation (enzymes, binding proteins)

    • Histone modifications (enzymes)

    • Specific epigenetic patterns

  • Associated Disorders:

    • Neurodevelopmental disorders

    • Mental diseases

Terminal Selectors as Transcriptional Regulators

  • Definition and Function:

    • Terminal selectors are critical transcription factors that regulate terminal effector genes necessary for neuronal identities and functions.

  • Regulation Mechanism:

    • Act as combinatorial transcriptional complexes to activate necessary genes for neurotransmitter production and other neuron functions.

Temporal and Sequential Transcriptional Dynamics in Corticogenesis

  • Research Contributions: Tanzila Mukhtar, Jeremie Breda, Manal A Adam, et al.

Spatial and Temporal Coordinates of Determination

  • Identity Formation in Neuroblasts:

    • Neuroblasts characterized by anterior-posterior positional identity genes determining their fate through expression of specific neuroblast proteins.

  • Example Genes:

    • Homeobox genes like vnd, ind, and msh distinguish neuroblasts along the ventral midline to dorsolateral extent.

Asymmetric Cell Division in Drosophila

  • Principle of Asymmetric Division:

    • One daughter cell becomes a ganglion mother cell (GMC), while the other continues as a neuroblast.

  • Control Mechanisms:

    • Initiated by cell polarity, distribution of cell fate determinants, and mitotic spindle orientation.

  • Key Components:

    • Numb, Miranda, and Prospero complexes are vital for ensuring asymmetric outcomes in cell division.

Photoreceptor Cell Fate in Drosophila Retina

  • Differentiation Process:

    • Retinal differentiation occurs via a wave-like progression from posterior to anterior regions.

  • Morphogenetic Furrow:

    • This groove, formed by cell constriction, is where ommatidial (compound eye unit) differentiation begins.

  • Sequential Assimilation into Ommatidia:

    • Cells progressively integrate into clusters as the wave of neurocrystallization advances.

Concluding Thoughts on Neural Development

  • Predictability of Cell Fate:

    • The interactive effects of intrinsic and extrinsic factors influence the determination of neural cell fates.