Disentangling cell-intrinsic and extrinsic factors underlying evolution.

Area of Science:

• Developmental biology
• Evolutionary biology
• Genetics

Background:

• Understanding cell and organ development requires distinguishing autonomous processes from those dependent on cell-cell or environmental interactions.
• Chimeras are crucial tools for classifying developmental processes as cell-intrinsic or extrinsic.

Purpose of the Study:

• To develop a quantitative framework for decomposing evolutionary divergence in traits into cell-intrinsic, extrinsic, and interaction components.
• To apply this framework to gene expression and cellular traits in interspecies chimeras.

Main Methods:

• Development of a novel conceptual framework to partition trait divergence.
• Analysis of gene expression in reciprocal rat-mouse chimeras.
• Investigation of neuronal differentiation and imprinted gene expression in chimeric models.

Main Results:

• The majority of gene expression divergence in rat-mouse chimeras is cell-intrinsic, with extrinsic factors playing a significant role.
• A rat extracellular environment can extrinsically up-regulate endoplasmic reticulum (ER) stress response pathways in specific cell types.
• Neuronal differentiation involves complex intrinsic-extrinsic factor interactions, and imprinted genes show mis-expression in species-mismatched environments.

Conclusions:

• The developed framework enables precise decomposition of evolutionary divergence in quantitative traits.
• Cell-intrinsic factors are dominant, but extrinsic influences are integral to developmental divergence and gene regulation.
• Imprinted gene mis-expression in chimeras may indicate evolving imprinting mechanisms contributing to interspecies barriers.