Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain

Abstract

Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary, and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior, and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.

Down-Regulation of Inpp5e Associated With Abnormal Ciliogenesis During Embryonic Neurodevelopment Under Inositol Deficiency

“…There was also an increasing peak of Inpp5e expression in the hindbrain of control group from E 10.5 to E 13.5, while no obvious trend was observed in the hindbrain of the NTDs group. These phenomena were probably due to the precise spatial-temporal specificity of gene expression during embryonic neurodevelopment ( 34 ). Notably, in the inositol-deficient mouse model, INPP5E was found to be markedly diminished among NTDs embryos compared with the controls at E 10.5, E 11.5, E 12.5, and E 13.5.…”

Spatial transcriptomic survey of human embryonic cerebral cortex by single-cell RNA-seq analysis

“…Previous studies, which have analyzed temporal and spatial neural development in rodent, human, and non-human primate brains, and have uncovered specific regional and temporal molecular characteristics of brain development, were almost based on bulk RNA-seq analysis. 19 – 24 The molecular profiles of each structure can be unveiled by analyzing micro-dissected cortical tissues. However, such assessments are far from revealing the detailed mechanisms of cerebral cortex organization, as dissected structures are still composed of multiple cell types.…”

Differential Spatiotemporal Expression of Type I and Type II Cadherins Associated With the Segmentation of the Central Nervous System and Formation of Brain Nuclei in the Developing Mouse

“…The present study examines mRNA expression levels of classical type I and type II cadherins and the atypical Cdh13 throughout the developing mouse CNS [from embryonic day (E) 11.5 to postnatal day (P) 56], with the goal of identifying morphogenetic events regulated by cadherin-mediated differential cell–cell adhesion. Cadherins mRNA expression levels in each anatomical structure were obtained from in situ hybridization (ISH) studies carried out at the Allen Institute for Brain Science 1 and available through the Allen Developing Mouse Brain Atlas 2 ( Lein et al, 2007 ; Ng et al, 2009 ; Thompson et al, 2014 ; Chou et al, 2016 ). This neurodevelopmental atlas is comprised of detailed analysis of genome-wide mRNA abundance at a single-cell resolution level in each neuroanatomical structure defined by the ontological organization of the mouse CNS ( Dong, 2008 ; Watson et al, 2011 ) and described in the Reference Mouse Brain Atlas 3 .…”