Apoptosis and Animal Development

Programmed Cell Death (Apoptosis)

• Apoptosis is an active cellular process leading to cell death.
• It's a normal, controlled part of growth and development.
• It's a way for the body to get rid of unwanted or abnormal cells.
• The word "apoptosis" comes from the Greek word for "falling off" (like leaves from a tree).
• It's different from accidental cell death (necrosis).

Animal Development and Cell Death

• Animal development starts with rapid proliferation of embryonic cells.
• These cells differentiate into specialized cell types making up tissues and organs.
• Humans have approximately 10¹⁴ cells and over 200 different cell types.
• Development involves a balance between cell proliferation and cell death.

Cell Renewal

• Cell death must be balanced by cell renewal in adult organisms.
• Most tissues contain stem cells that replace lost cells.
• Stem cells' ability to proliferate and differentiate is crucial for replacing damaged tissues.

Apoptosis vs Necrosis

• Apoptosis is a controlled process.
• Necrosis is a process caused by irreversible cell injury.
• Apoptotic cells are removed efficiently and don't trigger inflammation.
• Necrotic cells cause an inflammatory response and a release of contents into the extracellular space.

Programmed Cell Death Pathways

• Two main pathways: intrinsic and extrinsic.
• Intrinsic pathway: triggered by internal signals, DNA damage, or exposure to certain chemicals.
• Extrinsic pathway: triggered by signals from other cells.

Central Regulators of Apoptosis (Bcl-2 Family)

• Bcl-2 family members have different roles in apoptosis.
• Antiapoptotic proteins (e.g., Bcl-2, Bcl-xL) prevent apoptosis.
• Proapoptotic proteins (e.g., Bax, Bak) promote apoptosis.

Apoptosis in Different Scenarios

• Virus-infected cells undergo apoptosis to prevent virus spread.
• DNA damage can trigger apoptosis to eliminate potentially cancerous cells.
• Neuron development involves programmed cell death for proper connections.
• Cell survival is dependent on growth factors, neighboring cell contact, and extracellular matrix.

Apoptosis Mechanisms and Details

• In apoptosis, cells shrink and break into apoptotic bodies.
• Apoptotic bodies are phagocytosed (engulfed) by neighboring cells.
• Phosphatidylserine (PS) expression on the surface of apoptotic cells signals macrophages for removal.

Signs and Signals of Apoptosis

• Cytochrome C release from mitochondria is a key event in the intrinsic pathway.
• Caspases (a family of proteases) are central to the execution of apoptosis.

Intrinsic Pathway

• Initiated by a withdrawal of survival signals from the environment
• Includes factors like lymphokines (e.g., interleukin-2), nerve growth factor, and extracellular matrix.

Extrinsic Pathway

• Initiated by signals from other cells, such as cytotoxic T lymphocytes.
• Involves Fas ligand binding to Fas receptors on the target cell to initiate apoptotic cell death.