Developmental and Human Embryology: Cell-Cell Communication

Cadherins:
- Definition: Calcium-dependent adhesion molecules that are critical for establishing and maintaining inter-cellular connections.
- Function: Crucial for the spatial segregation of different cell types.
- Illustrated in Figure 4.6.

The strength of cadherin interactions leads to differences in:
- Cell surface tension.
- The tendency of cells to bind together.
Steinberg (2005) study insights:
- In the study, two sub-clones were identified:
- One sub-clone with 2.4 times more cadherins after 4 hours and 24 hours.
- Question: Which sub-clone had greater surface tension?
Understanding sorting:
- Sorting depends on the levels of cadherins present on the cell surfaces.
- Example: R = P-cadherin: Green = E-cadherin.

Environmental Coordination:
- Cell-to-cell interactions do not occur in isolation; they require environmental context, specifically the extracellular matrix (ECM).
Extracellular Matrix (ECM):
- Definition: An insoluble network composed of macromolecules secreted by cells into their environment.
- Components:
- Collagen.
- Proteoglycans.
- Specialized glycoproteins (e.g., laminins and fibronectins).
- Basal Lamina: A specific type of ECM consisting of collagen IV and laminin.

ECM is fundamental for:
- Cell adhesion.
- Cell migration.
- The formation of epithelial sheets and tubules.
Functions of ECM:
- Provides directional movement or developmental signals.
- Contains integrin receptors that bind ECM molecules.

Integrins:
- Definition: Key receptors that bind ECM molecules, crucial for cellular processes such as adhesion and signaling.
- RGD Sequence: A specific sequence (arginine-glycine-aspartate) that is recognized by integrins.

Definition of EMT:
- An orderly series of events in which epithelial cells are transformed into mesenchymal cells.
- Integration of multiple topics related to cell behavior and development.

Throughout development, signaling is essential for regulating:
- Cell differentiation.
- Cell behavior, such as changing shape or mitotic rates.
- The fate of neighboring cells.
Induction: Interaction that occurs at close range between two or more cells or different tissues, resulting in changes in behavior:
- Components of Inductive Signal:
1. Inducer: The tissue that produces the signal influencing another tissue’s behavior — often a paracrine factor (proteins made by one group of cells that alter neighboring cells).
2. Responder: The tissue being influenced, which contains specific receptors for the inductive signals.
- Competence: The ability of a tissue to respond to an inductive signal.

Example: Ectodermal competence in relation to the optic vesicle inducer in Xenopus.
- Induction can give tissues the competence to respond to additional inductive signals.
Transplant Experiments:
- Demonstrated additive effects of inducers in lens induction involving endoderm, mesoderm, neural plate, and optic vesicle development.

Reciprocal Inductions: When the responding tissue becomes an inducer itself, influencing the original inducer.
Types of Inductive Interactions:
- Instructive Interaction: A signal from the inducing cell is necessary for initiating new gene expression in the responding cell.
- Permissive Interaction: The responding tissue has already been specified and only requires an appropriate environment for expressing traits.

Example of Regional Specificity: Feather induction in chicks, where dermal mesenchyme controls regional specificity for competent epidermal epithelium.
Example of Genetic Specificity: Ectoderm structures in amphibians respond to inducers but can only form structures that align with their genetic possibilities.

Juxtacrine: Involves cell membrane proteins on one cell that interact with receptors on adjacent cells.
Paracrine: Proteins synthesized by one cell, released to induce effects on nearby cells.
Autocrine: A factor secreted by a cell that acts on the same cell.
Endocrine: Factors such as hormones that travel through the bloodstream to exert effects.

Morphogen: Definition of a diffusible biochemical that can influence cell fate based on its concentration.
Key Role in Gene Expression: This gradient influences the regulatory mechanisms in cell fate specification.

Organ induction is controlled by a limited set of paracrine factors, categorized into four major families:
1. FGF (Fibroblast Growth Factor)
2. Hedgehog
3. Wnt
4. TGF-β (Transforming Growth Factor Beta)
Mechanism of Action: Paracrine factors bind to receptors, triggering enzyme cascades leading to transcription factor regulation or cytoskeletal changes (Signal Transduction Cascades).

FGF Factors and RTK Pathway:
- FGFs are paracrine factors, comprising about 24 structurally related members.
- They can produce multiple isoforms, acting through FGFRs (Fibroblast Growth Factor Receptors).
Specific FGF Example: Fgf8 plays an important role in limb and lens development.

RTKs such as FGFRs work through signal cascades:
- Ras Pathway: A significant signaling pathway involved in cell growth and differentiation.
- Jak-Stat Pathway: Another pathway influencing transcription and cellular responses.

Vertebrates have three homologs associated with the Hedgehog signaling pathway: Shh, Dhh, and Ihh. Shh plays the most critical developmental role.
Experimental Insight: Observations from Veratrum californicum, a plant that produces an alkaloid substance inhibiting Shh production.

Comprises at least 15 members, contributing to various developmental functions.
Notably connected to the fly gene 'Wingless', leading to the differentiation of 'canonical' and 'non-canonical' pathways.

A large group comprising more than 30 structurally related members with multiple biological roles.

Notable Juxtacrine Factors:
- Notch: Binds to delta, jagged, or serrate proteins.
- Eph Receptors: Interact with ephrin ligands to aid in juxtacrine communication.