Distinct requirements for Tcf3 and Tcf12 during oligodendrocyte development in the mouse telencephalon.

Background: E-proteins encoded by Tcf3, Tcf4, and Tcf12 are class I basic helix-loop-helix (bHLH) transcription factors (TFs) that are thought to be widely expressed during development. However, their function in the developing brain, specifically in the telencephalon remains an active area of research. Our study examines for the first time if combined loss of two E-proteins (Tcf3 and Tcf12) influence distinct cell fates and oligodendrocyte development in the mouse telencephalon.

Olig2 defines a subset of neural stem cells that produce specific olfactory bulb interneuron subtypes in the subventricular zone of adult mice.

Distinct neural stem cells (NSCs) reside in different regions of the subventricular zone (SVZ) and generate multiple olfactory bulb (OB) interneuron subtypes in the adult brain. However, the molecular mechanisms underlying such NSC heterogeneity remain largely unknown. Here, we show that the basic helix-loop-helix transcription factor Olig2 defines a subset of NSCs in the early postnatal and adult SVZ.

Generation of a Mouse Model to Study the Noonan Syndrome Gene in the Telencephalon.

The leucine zipper-like transcriptional regulator 1 () is a BTB-Kelch domain protein involved in RAS/MAPK pathway regulation. Mutations in are associated with cancers and Noonan syndrome, the most common RASopathy. The expression and function of in the developing brain remains poorly understood.

A role for sustained MAPK activity in the mouse ventral telencephalon.

The MAPK pathway is a major growth signal that has been implicated during the development of progenitors, neurons, and glia in the embryonic brain. Here, we show that the MAPK pathway plays an important role in the generation of distinct cell types from progenitors in the ventral telencephalon. Our data reveal that phospho-p44/42 (called p-ERK1/2) and the ETS transcription factor Etv5, both downstream effectors in the MAPK pathway, show a regional bias in expression during ventral telencephalic development, with enriched expression in the dorsal region of the LGE and ventral region of the MGE at E13.

Analysis of reactive astrogliosis in mouse brain using hybridization combined with immunohistochemistry.

Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries. Here, we present a revised hybridization and immunohistochemistry (IHC) protocol to label the reactive astrocytes in the mouse brain. Several approaches for quantifying astrocyte reactivity lacked sensitivity to discriminate across the spectrum.

AMPK-Regulated Astrocytic Lactate Shuttle Plays a Non-Cell-Autonomous Role in Neuronal Survival.

Lactate is used as an energy source by producer cells or shuttled to neighboring cells and tissues. Both glucose and lactate fulfill the bioenergetic demand of neurons, the latter imported from astrocytes. The contribution of astrocytic lactate to neuronal bioenergetics and the mechanisms of astrocytic lactate production are incompletely understood.

Gsx transcription factors control neuronal versus glial specification in ventricular zone progenitors of the mouse lateral ganglionic eminence.

The homeobox gene Gsx2 has previously been shown to inhibit oligodendroglial specification in dorsal lateral ganglionic eminence (dLGE) progenitors of the ventral telencephalon. The precocious specification of oligodendrocyte progenitor cells (OPCs) observed in Gsx2 mutants, however, is transient and begins to normalize by late stages of embryogenesis. Interestingly, this normalization correlates with the expansion of Gsx1, a close homolog of Gsx2, in a subset of progenitors in the Gsx2 mutant LGE.

Characterization of Glcci1 expression in a subpopulation of lateral ganglionic eminence progenitors in the mouse telencephalon.

Background: The lateral ganglionic eminence (LGE) in the ventral telencephalon is a diverse progenitor domain subdivided by distinct gene expression into a dorsal region (dLGE) that gives rise to olfactory bulb and amygdalar interneurons and a ventral region (vLGE) that gives rise to striatal projection neurons. The homeobox gene, Gsx2, is an enriched marker of the LGE and is expressed in a high dorsal to low ventral gradient in the ventricular zone (VZ) as development proceeds. Aside from Gsx2, markers restricted to the VZ in the dLGE and/or vLGE remain largely unknown.

Selective neuronal expression of the SoxE factor, Sox8, in direct pathway striatal projection neurons of the developing mouse brain.

The striatum is the major component of the basal ganglia and is well known to play a key role in the control of motor function via balanced output from the indirect (iSPNs) and direct pathway striatal projection neurons (dSPNs). Little is known, however, about the molecular genetic mechanisms that control the formation of the iSPNs versus dSPNs. We show here that the SoxE family member, Sox8, is co-expressed with the dSPN markers, Isl1 and Ebf1, in the developing striatum.

The protein tyrosine phosphatase Shp2 is required for the generation of oligodendrocyte progenitor cells and myelination in the mouse telencephalon.

The protein tyrosine phosphatase Shp2 (PTPN11) is crucial for normal brain development and has been implicated in dorsal telencephalic neuronal and astroglia cell fate decisions. However, its roles in the ventral telencephalon and during oligodendrogenesis in the telencephalon remain largely unknown. Shp2 gain-of-function (GOF) mutations are observed in Noonan syndrome, a type of RASopathy associated with multiple phenotypes, including cardiovascular, craniofacial, and neurocognitive abnormalities.

MELK-dependent FOXM1 phosphorylation is essential for proliferation of glioma stem cells.

Glioblastoma multiforme (GBM) is a life-threatening brain tumor. Accumulating evidence suggests that eradication of glioma stem-like cells (GSCs) in GBM is essential to achieve cure. The transcription factor FOXM1 has recently gained attention as a master regulator of mitotic progression of cancer cells in various organs.