Regeneration Processes in Animals

Developmental Biology - Lesson 29 & 30

• Regeneration Defined: Reactivation of development in postembryonic life to restore missing or damaged tissues.
• Comparative Regenerative Capabilities: Different organisms exhibit varying abilities to regenerate. Plants can regenerate entire plants from a single cell, whereas mammals can regenerate some tissues and organs but not usually whole appendages. Hydra and planaria can regenerate entire bodies.
• Regeneration in Mammals: Individual tissues and organs within mammals possess varying regenerative capabilities.
• Steps of Regeneration:
  • Pre-injury: Organisms maintain a "morphological memory map" of their cells and tissues' identity and position.
  • Post-injury: Cells recognize the injury and need for replacement, followed by rapid wound closure.
  • Regenerative response: Embryonic-like mechanisms facilitate cell proliferation, tissue growth, and cell patterning for structure restoration.
  • Completion: Regeneration halts when the correct size and shape of the structure are achieved and integrated into the organism.
• Regeneration Modes:
  • Stem Cell-Mediated: Stem cells regenerate tissues like hair and blood cells.
  • Epimorphosis: Undifferentiated cells (blastema) regenerate structures (e.g., amphibian limbs).
  • Morphallaxis: Re-patterning existing tissues with little new growth, like in hydra, involves cell death and transdifferentiation.
  • Compensatory: Differentiated cells divide while maintaining their function to regenerate (mammalian liver).
• Regeneration and Embryonic Development: Regeneration shows a dual nature, leveraging embryonic mechanisms while adapting to postembryonic constraints. Key differences include immune responses and reprogramming of adult cells. Tissue integration, size control, and termination are crucial.
• Plants and Animal Regeneration:
  • Plants: Extreme plasticity allows regeneration of tissues and even entire organisms (e.g., totipotent cells, meristems). Regeneration responses to injuries like shoot or root formation.
  • Animals: Regeneration traits are diverse. Acoels and planaria exhibit complete regeneration. Sponges possess regenerative abilities including totipotency and mechanisms like stem cell-mediated regeneration and transdifferentiation (morphallaxis). Specific processes exist that relate to the ability to regenerate.
• Sponge Choanocytes: These cells proliferate in response to injury, highlighting tissue regeneration response in sponges.
• Evolutionary Conservation in Regeneration: Regeneration-responsive enhancers (RREs) are conserved sequences controlling injury and regeneration response genes. This might explain why some species have retained regenerative abilities.
• Natural Selection Affecting Regeneration: Natural selection may favor rapid scarring over regeneration to prevent life-threatening blood loss. Risk of cancer associated with rapid cell division may also mitigate regeneration.
• Whole-Body Animal Regeneration: -Hydras and Planarians regenerate entire bodies via mechanisms similar to asexual reproduction. -Hydras feature two epithelial layers (ectoderm, endoderm) and multipotent interstitial stem cells (ISCs) for consistent regeneration. -Hydra cells (ISCs) differentiate into various cell types including neurons, nematocytes, and gland cells in response to injury or loss of body parts. -Regeneration in hydra is a continuous processes using shared progenitors for different cell types.
• The Head Activator in Hydra: Hydra body segments can regenerate heads and feet, controlled by morphogenetic gradients. Grafting experiments reveal head and foot activation gradients. Tissue from higher gradient regions shows a greater ability to induce head formation.
• Wnt/β-catenin Signaling During Hydra Budding: Wnt proteins act as head inducers, crucial for Hydra regenerative processes. Mutations or blocking the Wnt pathway influence the way regeneration occurs. The mechanism of how these signals lead to specific responses is also well investigated.
• Stem Cell-Mediated Regeneration in Flatworms: Planarians use pluripotent stem cells (neoblasts) in asexual reproduction. Cutting planarians results in both ends regenerating the missing parts.
• Flatworm Regeneration and its Limits: Planarians can regenerate their anterior and posterior ends, but some segments show difficulty regenerating completely due to the lack of morpgenen gradients.
• Blastema Formation and Cell Production During Planarian Regeneration: The blastema is a mass of undifferentiated cells found at the wound site that promotes tissue regeneration. Pluripotent neoblasts and cNeoblasts (clonogenic) regenerate cells crucial for function.
• Wnt Signaling in Planarian Regeneration: These signaling pathways are crucial for defining the tail and head regions in planarian regeneration to ensure correct tissue repair. Blocking Wnt signaling leads to unusual dual-headed or multiple structures along the body.
• Restoration of Head Regeneration in Planarians: Wnt/β-catenin signaling is vital for normal head regeneration. Blocking or altering it produces abnormal forms.
• Positional Control in Planarian Regeneration: Muscle fiber orientations dictate positional control gene expression crucial for proper regeneration.
• Overall Model for Planarian Regeneration: Tissue homeostasis, injury, reset of cell patterns, gradients, and the specification of positional cells and tissues within the regeneration process are tightly regulated.
• Bioelectric Regulation of Planarian Regeneration: Bioelectrical signals are proposed as an alternative to 'morphological memory maps" for cells within these organisms. Changes in voltage potential (Vmem) are critical, where different regions have different voltage levels.
• Bioelectric Interactions with Wnt/β-catenin Signaling: Bioelectrical signals influence positional control gene expression for proper regeneration, interacting with gene signaling.
• Tissue-Restricted Animal Regeneration in Axolotl: Salamanders possess epimorphic limb regeneration which allows limbs to regrow after amputation along the proximal-distal axis.
• Axolotl Limb Regeneration and Connective Tissue: Specialized connective tissue cells called fibroblasts specifically move through the regeneration blastema which is required for complete regeneration of the limb.
• Cells of the Connective Tissues: Specialized cells form the blastema and play a critical role in regeneration, particularly in instances of limb or tissue regeneration.
• Axolotl Regeneration and Incompetent Frogs: Post-metamorphic frogs struggle to regrow tissue and limbs and exhibit different gene expression to axolotls. The differences in these processes are critical to understanding the mechanistic basis of regeneration pathways.
• Blastema Cells Speciation: Blastema cells maintain tissue-specific identities even during dedifferentiation, essential for regeneration.
• Nerve Requirement for Axolotl Limb Regeneration: Nerves are vital for regeneration, Neuregulin (Nrg1) rescuer regeneration after denervation, suggesting nerves promote regenerative capacity.
• Induction of Ectopic Limbs in Salamanders: Nerve signals and the apical epidermal cap (AEC) are critical for correct blastema formation, crucial for complete limb generation. Accessory limbs can also be induced with appropriate signaling cues.
• Lens Regeneration in Newts: Dorsal pigmented epithelial cells (PECs) in newts undergo transdifferentiation to become lens cells; ventral PECs don't participate. Lens regeneration doesn't follow the standard embryological pathway.
• Mechanisms of Regeneration in Zebrafish: Zebrafish are critical models for studying regeneration in diverse organs. Wnt Beta-catenin signaling is crucial for blastema proliferation for regeneration, with interplay with other important pathways also observed.
• Spatiotemporal Requirements of Wnt/ß-catenin Signaling: Ubiquitin (global expression), Her4.3 (osteoblast progenitors), and DOX are important molecules to investigate the mechanisms regulating fin regeneration. -Regeneration in Mammals (Liver): Liver regeneration is a compensatory process where remaining liver lobes enlarge to restore function after partial hepatectomy. Various signaling pathways contribute to this process. -Liver Regeneration & Gene Expression: Gene expression changes in relation to increases in liver mass correlate with DNA synthesis peaking in the presence of specific cells in the liver, indicating a dynamic interplay during compensatory regeneration.