Molecular Analysis of Early Neural Plasticity - PROJECT SUMMARY
The development of a functional organ system during embryogenesis not only requires that cells adopt an
appropriate cell identity and pattern, but also the ability to maintain this identity and morphology in the face of
ongoing genetic and environmental perturbations that occur throughout embryogenesis. This ability to recover
from potentially disruptive alterations in development is referred to as plasticity or regulative ability. While all
cells possess some degree of plasticity in order to adapt to adverse conditions, pronounced plasticity is feature
of embryos. While there has been enormous progress in elucidating the molecular-cellular processes
governing normal development, there has been relatively less focus on elucidating the mechanisms governing
the extended process of regulation following a developmental perturbation, despite its clear importance for a
comprehensive understanding of development as well as its implications for regenerative medicine. Here we
employ the classic amphibian embryological system of Xenopus laevis to examine the regulative ability of the
presumptive nervous system during early embryogenesis. Previous experiments from our lab have
demonstrated that when the presumptive neural plate is removed from a mid-gastrula-stage embryo, rotated
180o, and transplanted back into a host embryo from which the equivalent region was removed, there is a near
total recovery, with the resulting embryo giving rise to a nervous system with appropriate regional gene
expression and functional capabilities. This regulative ability diminishes considerably by late gastrula stages. In
an effort to determine the molecular basis of this early developmental plasticity, we conducted a global gene
expression, RNA-Seq experiment on control embryos and embryos with rotated neural tissue. Our RNA-Seq
data suggest a model in which specific aspects of early neural plasticity are associated with a unique signature
of pathways and genes. The ability for transplanted tissue to incorporate and heal entails the upregulation of
apoptosis, ubiquitination, and oxidative stress, and specific ion flux pathways while the ability to recover from
rotation of neural tissue and re-patterns the anterior-posterior axis involves calcium homeostasis, chromatin
remodeling, neuronal transcription factor, and recognition molecule genes. In our first specific aim we will
obtain the temporal and spatial mRNA expression profiles of genes identified from RNA-Seq data to determine
if their expression patterns are consistent with a role for mediating specific aspects of early neural plasticity.
Our second aim will determine whether the candidate genes—whose expression patterns are consistent with
playing a role in early embryonic plasticity—functionally mediate regulative behavior of early neural tissue by
conducting gene knock-out/knockdown and overexpression assays. Taken together these data will provide
new insights into the plasticity and regulative behavior of the early embryonic nervous system that may have
important implications for understanding a fundamental and near universal feature of embryos as well as for
regenerative medicine.
