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.