Scaling of gene transcriptional gradients with brain size across mouse development.

The structure of the adult brain is the result of complex physical mechanisms acting in three-dimensional space through development. Consequently, the brain's spatial embedding plays a key role in its organization, including the gradient-like patterning of gene expression that encodes the molecular underpinning of functional specialization. However, we do not yet understand how changes in brain shape and size that occur across development influence the brain's transcriptional architecture. Here we investigate the spatial embedding of transcriptional patterns of over 1800 genes across seven time points through mouse-brain development using data from the Allen Developing Mouse Brain Atlas. We find that transcriptional similarity decreases exponentially with separation distance across all developmental time points, with a correlation length scale that follows a power-law scaling relationship with a linear dimension of brain size. This scaling suggests that the mouse brain achieves a characteristic balance between local molecular similarity (homogeneous gene expression within a specialized brain area) and longer-range diversity (between functionally specialized brain areas) throughout its development. Extrapolating this mouse developmental scaling relationship to the human cortex yields a prediction consistent with the value measured from microarray data. We introduce a simple model of brain growth as spatially autocorrelated gene-expression gradients that expand through development, which captures key features of the mouse developmental data. Complementing the well-known exponential distance rule for structural connectivity, our findings characterize an analogous exponential distance rule for transcriptional gradients that scales across mouse brain development, providing new understanding of spatial constraints on the brain's molecular patterning.

Acute and chronic effect of dietary phosphorus restriction on protein expression in young rat renal proximal tubules.

Renal proximal tubules play a vital role in phosphorus (P) homeostasis. It is well known that dietary P restriction up-regulates the activities of 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1-OHase), an enzyme that is involved in activation of vitamin D and thereby maintaining P balance. However, the mechanism involved in such regulation is not known. In the present study, we aim to identify proteins that might be involved in the renal adaptation to dietary P restriction using a proteomic approach. Renal proximal tubules were harvested from young rats fed either normal P diet or low P diet (LPD) for 1 to 7 days. Western blotting analysis of 1-OHase and signaling proteins in insulin-like growth factor I axis indicated an increase in expression of these proteins upon dietary P restriction. Using two-dimensional electrophoresis, we found that LPD reduced the total number of protein species expressed in renal proximal tubules. Differentially expressed proteins were analyzed and located using the software Melanie III, and their identities were found using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Our results showed that beta-actin, gamma-actin, major urinary protein, phosphatidylinositol transfer protein beta isoform, and G1/S-specific cyclin D3 are up-regulated and nonspecific lipid transfer protein is down-regulated by LPD.