Growth and Post-embryonic Development Notes

Post-embryonic development is characterized by growth, metamorphosis, and regeneration.
Embryonic development focuses on establishing the basic form and the primary body pattern of the organism.
Post-embryonic development involves - Growth: Defined as an increase in size or mass. - Metamorphosis: The transition from a larva to an adult form (e.g., $Larva \rightarrow Adult$ ). This process is characterized by the disappearance of old organs and the appearance of new organs. - Regeneration: This can occur in the juvenile or adult stage and involves the replacement of tissues or entire organs.

The lecture material covers content from Wolpert Chapter 13.
Specific sections include: - Growth: Chapters $13.1$ , $13.2$ , and $13.5$ . - Molting and Metamorphosis: Chapter $13.13$ . - Regeneration: Chapters $13.14$ through $13.16$ .

The determined post-embryonic stage influences both organ size and overall body size.
Growth occurs through three primary mechanisms which relate to cell proliferation, cell enlargement, and the accretion of extracellular material.

Definition: Increase in cell number through the process of mitosis.
Net Growth Calculation: Growth is determined by the balance between mitosis (cell birth) and apoptosis (programmed cell death).

Definition: An increase in the size of individual cells rather than an increase in cell number.
Mammalian examples of hypertrophy include: - Heart - Kidney - Nerves

Definition: Increase in the extracellular space achieved by the secretion of Extracellular Matrix (ECM).
Common examples in structural tissues include: - Bone - Cartilage

Proliferation control is managed through Cyclins, which are checkpoint proteins.
The cell cycle phases include: - Interphase: Divided into $G_1$ , $S$ (Synthesis), and $G_2$ . - M Phase: Comprising Prophase, Prometaphase, Metaphase, Anaphase, Telophase, and Cytokinesis.
Cyclin and Cyclin-dependent kinase (Cdk) activity levels fluctuate to drive transitions: - $Cdk$ is inactive when not bound to the appropriate cyclin. - $G_1/S$ cyclin triggers the transition into the DNA synthesis phase ( $S$ phase). - $S$ cyclin maintains the cycle through synthesis. - $M$ cyclin triggers the transition into mitosis.
Checkpoints include: - Start Checkpoint: Occurs in late $G_1$ before entry into $S$ . - $G_2$ Checkpoint: Occurs after $S$ phase before entry into Mitosis. - Mitosis Checkpoint: Ensures proper cell division.
Cells can also enter a non-dividing state known as $G_0$ .

Cancer represents a fundamental mutation in cell division genes.
Prevalence: Approximately $85\%$ of cancers occur in the epithelia (e.g., gut and skin).
Mechanism: Epithelial tissues contain stem cells. Stem cell division is normally under tight regulation. Mutations that lead to continuous, unregulated division result in tumor progression.
Tumor Progression: This involves the accumulation of many mutations. For example, pancreatic cancer is associated with roughly $63$ specific mutations in proliferation genes.

Metamorphosis is triggered by environmental cues such as nutrition, temperature, and light.
Hormonal Pathway: - Environmental cues act on the Hypothalamus. - The Hypothalamus releases Corticotropin-Releasing Hormone (CRH). - CRH stimulates the Pituitary gland to release Thyroid-Stimulating Hormone (TSH). - TSH acts on the Thyroid to release thyroxine hormones: $T_4$ (Thyroxine) and $T_3$ (Triiodothyronine). - Positive feedback loops reinforce the production of these hormones to drive metamorphosis.
Hormonal Regulation: - Prolactin: Acts to delay metamorphosis. - $T_4$ and $T_3$ : Act to promote metamorphosis.
Tissue-Specific Hormone Effects: - Limb: Thyroid hormone leads to an increase ( $\uparrow$ ) in cell growth. - Tail: Thyroid hormone leads to a decrease ( $\downarrow$ ) in cell growth (leading to resorption).

Regeneration is the process where injuries are repaired, and tissues are replaced.
In adults, this includes maintenance and repair; in young organisms, it covers growth as well as repair.
Comparative Complexity: - Lower Vertebrates (Amphibians): Can regenerate complex structures including the brain, heart, limbs, retina, lens, jaw, and tail. - Mammals: Regeneration is limited to tissues like the gut, skin, and blood. If the liver is damaged, the remaining parts undergo compensatory growth (enlargement) to fill the functional requirement.

Examples include Planarians, Hydra, and Starfish.
In some species, asexual reproduction is nearly synonymous with regeneration, where a whole animal can fragment into multiple new individuals.
Hydra Specifics: - A head piece can make a new tail. - A tail piece can make a new head. - A body piece can regenerate both a head and a tail.

Morphallaxis: Regeneration occurs through the reorganization of existing cells with no new cells produced initially.
Epimorphosis: Regeneration involves the production of new cells via mitosis.

Limb regeneration in amphibians (e.g., salamanders) follows a specific sequence of dedifferentiation and growth.
Step-by-Step Procedure: 1. Amputation (Injury): The limb is lost. 2. Healing: Migration of epidermal cells over the wound surface to form the Apical Cap. 3. Dedifferentiation: Mature cells at the site undergo a transition to an immature state. Macrophages are essential for this stage. 4. Blastema Formation: A mass of undifferentiated (immature) cells forms under the apical cap. 5. Growth Stages of the Blastema: - Cone Stage: Initial blastema formation. - Notch Stage: Differentiation of new muscle, bone, and nerves begins. - Palette Stage: The regeneration structure flattens into a palette shape. - Digit Stage: Individual digits reform. 6. Redifferentiation: Immature cells transition back into mature, specialized cells.
Positional Values: If a limb is amputated distally (near the tip), only the distal part is regenerated. If amputated proximally (near the base), the entire limb is regenerated. The duration of the process varies (e.g., observations recorded at $7$ , $21$ , $25$ , $32$ , $42$ , and $70$ days).

A critical question in developmental biology is whether blastema cells are multipotent (can become any tissue) or lineage-restricted (can only become the tissue type they originated from).
The GFP Experiment: - Donor: Animal with cells expressing Green Fluorescent Protein ( $GFP^+$ ). - Method: Transplant $GFP^+$ cells to the forelimb of a non-GFP animal. Amputate the limb and follow the fate of the GFP-labeled cells during regeneration using tissue-specific markers.
Findings: The blastema is mostly lineage specific. - Dermis cells regenerate into dermis. - Cartilage cells regenerate into cartilage. - Muscle cells regenerate into muscle. - Schwann cells regenerate into Schwann cells. - Epidermis cells regenerate into epidermis.