Regeneration in the Era of Functional Genomics and Gene Network Analysis

The main question in regenerative biology is understanding how organisms can regrow tissues and recover function after injury, which some organisms can do while others cannot. The challenge is to describe the mechanisms of regeneration at the molecular level, with a dissection of the system-wide network of molecular interactions that allows for regeneration. Functional genomics, which has been used to understand gene regulatory networks (GRNs) in developing tissues, can also be applied to study the molecular mechanisms underlying regeneration. The study will focus on the central nervous system because the loss of function has particularly devastating consequences for an organism. The lamprey, a jawless vertebrate, has giant reticulospinal (RS) neurons whose large size and ability to regenerate make them particularly suited for a GRN analysis. Some lamprey RS neurons reproducibly fail to regenerate, presenting an opportunity for side-by-side comparison of gene networks that either promote or inhibit regeneration.

• 1
  Functional genomics can be used to elucidate gene regulatory networks (GRNs) in developing tissues, which, like regeneration, are complex systems, therefore, can also be applied to study the molecular mechanisms underlying the complex functions of regeneration.
• 2
  The lamprey is the only vertebrate for which sufficient experimental data exist to satisfy what the National Institute of Neurological Disorders and Stroke (NINDS) has specified as the definition of functional regeneration in the spinal cord after injury.
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  Regenerative capacity varies between individual giant RS neurons, but is remarkably reproducible. The most robust regeneration is consistently observed in mesencephalic cell M1, isthmic cell I2, and the auxiliary Mauthner; whereas the least regeneration is observed in isthmic cell I1, bulbar cells B1 and B3, and the Mauthner cell.