Promyelocytic leukemia zinc finger is involved in the formation of deep layer cortical neurons

Abstract

Background Promyelocytic leukemia zinc finger (Plzf), a transcriptional regulator involved in a lot of important biological processes during development, has been implied to maintain neural stem cells and inhibit their differentiation into neurons. However, the effects of Plzf on brain structures and functions are still not clarified. Results We showed that Plzf expression was detected as early as embryonic day (E) 9.5 in Pax6 + cells in the mouse brain, and was completely disappeared in telencephalon before the initiation of cortical neurogenesis. Loss of Plzf resulted in a smaller cerebral cortex with a decrease in the number of Tbr1 + deep layer neurons due to a decrease of mitotic cell number in the ventricular zone of forebrain at early developmental stage. Microarray, qRT-PCR, and flow cytometry analysis identified dysregulation of Mash1 proneural gene expression. We also observed an impairment of recognition memory in Plzf -deficient mice. Conclusions Plzf is expressed at early stages of brain development and involved in the formation of deep layer cortical neurons. Loss of Plzf results in dysregulation of Mash1, microcephaly with reduced numbers of early-born neurons, and impairment of recognition memory. Electronic supplementary material The online version of this article (10.1186/s12929-019-0519-8) contains supplementary material, which is available to authorized users.

Zbtb16 regulates social cognitive behaviors and neocortical development

“…Since cognitive impairment in the novel object recognition test in Zbtb16 KO mice (without age information) has been reported 21 , we also investigated the cognitive function of Zbtb16 KO mice in the same test. As we expected, we observed significant reductions in difference score ( P = 0.0122) and discriminant ratio ( P = 0.0032) of the novel object recognition test in Zbtb16 KO mice (Fig.…”

“…2 ). Since reduced neocortical area and abnormal deep layer formation of primary motor (M1) cortex in neonatal Zbtb16 KO mice have been reported 21 , we examined neocortical thickness and lamination in the S1 cortex of Zbtb16 KO mice at 7–8 weeks. The reduced brain size of Zbtb16 KO mice was observed as previously reported (Fig.…”

“…ZBTB16 is expressed in human embryonic stem cell (ES)-derived neural stem cells (NSC) and primary neural plate tissue, playing a role in maintenance, proliferation 19 , and neuronal differentiation 20 . A recent study has reported reduced cortical surface area and a number of deep-layer neurons in the neocortex of Zbtb16 lu/lu mutant mice at neonatal stages 21 . In addition, Zbtb16 lu/lu mutant mice showed an impairment of recognition memory in the novel object recognition test 21 .…”

“…A recent study has reported reduced cortical surface area and a number of deep-layer neurons in the neocortex of Zbtb16 lu/lu mutant mice at neonatal stages 21 . In addition, Zbtb16 lu/lu mutant mice showed an impairment of recognition memory in the novel object recognition test 21 . These studies indicate the involvement of Zbtb16 in neocortical development.…”

Zinc Finger Transcription Factor Zbtb16 Coordinates the Response to Energy Deficit in the Mouse Hypothalamus

“…During development, Zbtb16 plays a specific role of balancing the self-renewal and differentiation of stem cells in multiple organs (see (Liu et al, 2016) and references therein) but carries out diverse tissue-specific functions in adult. Nonetheless, the function of Zbtb16 has never been studied in adult brains while its expression and function have been described in developing central nervous system (Avantaggiato et al, 1995;Cook et al, 1995;Gaber et al, 2013;Lin et al, 2019). More careful expression analysis in the brain revealed Zbtb16 expression in two hypothalamic nuclei, the PVH and the ARC, that are critical for the control of energy balance.…”