Embryonic pericytes promote microglial homeostasis and their effects on neural progenitors in the developing cerebral cortex

AbstractDiverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels.

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Effect of riboflavin deficiency on development of the cerebral cortex in Slc52a3 knockout mice

Scientific Reports ◽

10.1038/s41598-020-75601-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Congyun Jin ◽

Atsushi Yonezawa ◽

Hiroki Yoshimatsu ◽

Satoshi Imai ◽

Madoka Koyanagi ◽

...

Keyword(s):

Cerebral Cortex ◽

Gene Disruption ◽

Radial Glia ◽

Neural Progenitors ◽

Cortical Layers ◽

Riboflavin Deficiency ◽

Proliferative Rate ◽

Neonatal Lethality ◽

Significant Difference ◽

The Brain

Abstract Riboflavin transporter 3 (RFVT3), encoded by the SLC52A3 gene, is important for riboflavin homeostasis in the small intestine, kidney, and placenta. Our previous study demonstrated that Slc52a3 knockout (Slc52a3−/−) mice exhibited neonatal lethality and metabolic disorder due to riboflavin deficiency. Here, we investigated the influence of Slc52a3 gene disruption on brain development using Slc52a3−/− embryos. Slc52a3−/− mice at postnatal day 0 showed hypoplasia of the brain and reduced thickness of cortical layers. At embryonic day 13.5, the formation of Tuj1+ neurons and Tbr2+ intermediate neural progenitors was significantly decreased; no significant difference was observed in the total number and proliferative rate of Pax6+ radial glia. Importantly, the hypoplastic phenotype was rescued upon riboflavin supplementation. Thus, it can be concluded that RFVT3 contributes to riboflavin homeostasis in embryos and that riboflavin itself is required during embryonic development of the cerebral cortex in mice.

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