Wang, J.-R. | Search bioRxiv

bioRxiv2019

Single cell transcriptomic analysis revealed long-lasting adverse effects of prenatal tamoxifen administration on neurogenesis in prenatal and adult brains

CreER/LoxP system has enabled precise gene manipulation in distinct cell subpopulations at any specific time point upon tamoxifen (TAM) administration. This system is widely accepted to track neural lineages and study gene functions. We have observed prenatal TAM treatment caused high rate of delayed delivery and mortality of pups. These substances could promote undesired results, leading to data misinterpretation. Here, we report that TAM administration during early stages of cortical neurogenesis promoted precocious neural differentiation, while inhibited neural progenitor cell (NPC) proliferation. The TAM-induced inhibition of NPC proliferation led to deficits in cortical neurogenesis, dendritic morphogenesis, and cortical patterning in neonatal and postnatal offspring. Mechanistically, single cell RNA sequencing (scRNA-seq) analysis combined with in vivo and in vitro assays showed TAM could exert these drastic effects mainly through dysregulating the expression of Dmrta2 and Wnt8b. In adult mice, administration of TAM significantly attenuated NPC proliferation in both the subventricular zone and the dentate gyrus. This study revealed the cellular and molecular mechanisms for the adverse effects of prenatal tamoxifen administration on corticogenesis, suggesting that tamoxifen-induced CreER/LoxP system may not be suitable for neural lineage tracing and genetic manipulation studies in both embryonic and adult brains. SignificantFor the first time, our study revealed the molecular mechanisms underlying tamoxifen activities on cortical development. This study also clearly showed that care must be taken when using tamoxifen-induced CreER/LoxP system for neural lineage tracing and genetic manipulation studies.

neuroscience↗

bioRxiv2017

An overexpressed Q allele leads to increased spike density and improved processing quality

Spike density and processing quality are important traits during the evolution of wheat, which is controlled by multiple gene loci. The associated gene loci have been heavily studied with slow progress. A common wheat mutant with extremely compact spikes and good processing quality was isolated. The gene (Qc1) responsible for the mutant phenotype was mapped and cloned, and the cellular mechanism for the mutant phenotype was investigated. Qc1 originated from a point mutation that interferes with the miR172-directed cleavage of the Q gene, leading to its overexpression. Qc1 reduces the longitudinal cell size of rachises, resulting in an increased spike density. Qc1 increases the number of vascular bundles, which suggests a higher efficiency in the transportation of assimilates in the spikes of the mutant than in the WT. This could account for the improved processing quality. The effects of Qc1 on spike density and wheat processing quality were confirmed by the identification of nine common wheat mutants having four different Qc alleles. These results deepen our understanding of the key role of Q gene, one of the most important domestication gene for wheat, and provide new insights for the potential application of Qc allele in wheat breeding.

genetics↗