Development of the nervous system

Neural Development Overview

  • Neural development refers to the biological processes involved in the formation of the human brain.

  • Induced pluripotent stem cell technology is utilized to create human brain models in vitro.

Human Brain Development

  • Blastocyst Stage (5 Days Post-Conception):

    • Consists of 24 to 322 cells.

    • Size is approximately 0.2mm.

    • Structures: trophectoderm, inner cell mass, blastocoel.

  • Brain Volume:

    • Ranges from 1180 to 1260 cm³.

    • Measures about 5.5 x 6.5 x 3.6 inches (140 x 167 x 93 mm).

    • Weight is about 3 pounds (1.3 kg).

  • Cell Composition:

    • Approximately 86 billion neurons.

    • Estimated 5-10 times more glial cells, totaling between 516 billion and 946 billion cells.

Development Process from Fertilization to Blastocyst

  • Fertilization:

    • The fusion of haploid gametes (sperm and oocyte) forms a diploid zygote.

  • Morula Stage:

    • A mass of blastomeres formed from the zygote by cleavage (rapid cell divisions).

    • Named for its resemblance to a mulberry.

  • Blastocyst Formation:

    • Comprises many blastomeres which develop into the blastula and eventually the blastocyst.

Gastrulation and Germ-Layer Formation in Frogs

  • Gastrulation Process:

    • Involves the reorganization of blastomeres into three germ layers: endoderm, mesoderm, and ectoderm.

    • Cellular movements create new tissue relationships.

  • Gastrula Structure:

    • A transient developmental structure that contains all three germ layers.

Neural Induction Experiments

  • Animal Cap Isolation:

    • Isolating fragments from embryos at various development stages reveals commitment to neural lineage.

    • Early isolation leads to epidermis development; later isolation during gastrulation leads to neural tissue development.

  • Spemann-Mangold Experiment:

    • Identified the organizer or inducer as a tissue part that instructs neighbors to develop specific tissues.

Key Discoveries in Neural Induction Factors (1992)

  • Normal development of Xenopus embryos shows dorsal structure patterns before gastrulation.

  • UV Light Treatment:

    • Disrupts dorsal inducing molecule arrangement.

  • Lithium Treatment:

    • Promotes development of dorsal tissues.

  • Rescue Infusion:

    • Injection of mRNA from dorsalized embryos can rescue UV-treated embryos.

  • Noggin Gene:

    • Isolated and shown to induce neural tissue formation without mesoderm induction.

Neurulation Process in Frogs

  • Neurulation involves the invagination of neuroectoderm cells to form the neural tube, a transient developmental structure.

Neurodevelopment Process After Neural Tube Formation

  • Key brain regions:

    • Hindbrain: Includes the mesencephalon and myelencephalon.

    • Forebrain: Comprises the prosencephalon with telencephalon and diencephalon.

  • Central Canal and Ventricle Formation:

    • Leads to spatial organization of future neural structures.

Anatomical Terminology in Neural Development

  • Directional Terms:

    • Anterior (front), Posterior (back), Superior (above), Inferior (below), Medial (middle), Lateral (edge), Dorsal (top/back), Ventral (bottom/front), Rostral (front/top of brain), Caudal (back/bottom of brain).

Segmentation Genes and Development in Drosophila

  • Molecular Gradients:

    • Maternal effect genes influence gap genes, which then activate segment polarity genes, controlling segment identity.

  • Homeotic Genes:

    • Define specific segment identities in embryos.

Hox Gene Clusters and Their Role in Development

  • Spatial Organization:

    • Similar patterns in Drosophila and vertebrates; expression order is crucial for proper segment identification.

    • Hox clusters control hindbrain development among others.

Neural Stem Cell Properties and Developmental Processes

  • Interkinetic Nuclear Migration:

    • Involves migration of neural progenitor cells throughout embryonic development.

  • Radial and Basal Progenitor Cells:

    • Cells migrate from ventricular zone to cortical plate, contributing to brain structure.

Inside-Out Cortical Development

  • Neurons generated in a sequential manner lead to distinct cortical layers, with early neurons migrating past older neurons.

  • Reelin's Function:

    • Plays a crucial role in the proper layering of developing neurons; disruption leads to reversed layering in Reeler mice.

Birthdating Studies and Neurogenesis

  • Proliferation and Differentiation:

    • Stem cells can either remain self-renewing or differentiate into mature neurons, astrocytes, or oligodendrocytes.

    • Birth dates of cells are traced through injections in pregnant female models to study neural population dynamics.

Mechanisms of Asymmetric Cell Division

  • Polarized Cell Divisions:

    • Determinants for cell fate are unevenly distributed during divisions, leading to specific cellular outcomes.

  • Oscillatory Gene Expression:

    • Proneural gene expression gives rise to neuron or glial fates through rhythmic expression patterns.

Factors Regulating Neuronal and Astrocyte Development

  • Various signaling pathways (e.g., FGF, Notch) impact the development and differentiation of neurons and astrocytes in vivo.