The subventricular zone (SVZ) in the neonatal mammalian forebrain simultaneously generates olfactory interneurons, astrocytes, and oligodendrocytes. The molecular cues that enable SVZ progenitors to generate three distinct cell lineages without a temporal switching mechanism are not known. Here, we demonstrate that the basic helix-loop-helix transcription factor Olig2 plays a central role in th...

During neural development, billions of neurons differentiate, polarize, migrate and form synapses in a precisely choreographed sequence. These precise developmental events are accompanied by discreet transitions in cellular polarity. While radial glial neural stem cells are highly polarized, transiently amplifying neural progenitors are less polarized after delaminating from their parental stem...

Postmitotic neurons are produced from a pool of cycling progenitors in an orderly fashion that requires proper spatial and temporal coordination of proliferation, fate determination, differentiation and morphogenesis. This probably relies on complex interplay between mechanisms that control cell cycle, specification and differentiation. In this respect, we have studied the possible implication ...

The directed differentiation of forebrain neuronal types from human embryonic stem cells (hESCs) has not been achieved. Here, we show that hESCs differentiate to telencephalic progenitors with a predominantly dorsal identity in a chemically defined medium without known morphogens. This is attributed to endogenous Wnt signaling, which upregulates the truncated form of GLI3, a repressor of sonic ...

The brain plays a central role in controlling energy, glucose, and lipid homeostasis, with specialized neurons within nuclei of the mediobasal hypothalamus, namely the arcuate (ARC) and ventromedial (VMH), tasked with proper signal integration. Exactly how the exquisite cytoarchitecture and underlying circuitry becomes established within these nuclei remains largely unknown, in part because hyp...

In the neurogenic phase of CNS development, the proliferating progenitors are found medially within the neuroepithelium. The adherens junctions on the apical membrane of proliferating neural progenitors allow for cell-cell adhesion and medial stratification. In contrast, differentiating neuronal precursors delaminate and migrate laterally, establishing the laminar layers. Apical adherens juncti...

Nicotinic acid adenine dinucleotide phosphate (NAADP) is an endogenous Ca(2+) mobilizing nucleotide presented in various species. NAADP mobilizes Ca(2+) from acidic organelles through two pore channel 2 (TPC2) in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differ...

Identification of multipotent progenitors has been difficult due to their rarity in adults. Here, we report a novel type of neuroepithelial myogenic progenitor that can be isolated from adult murine skeletal muscle. In culture, these progenitors generated radial glia-like cells that initiated mosaic myotubes, and subsequently developed into embryonic/fetallike myoblasts capable of robust myofib...

During embryonic development, the telencephalon is specified along its axis through morphogenetic gradients, leading to the positional-dependent generation of multiple neuronal types. After embryogenesis, however, the fate of neuronal progenitors becomes more restricted, and they generate only a subset of neurons. Here, we review studies of postnatal and adult neurogenesis, challenging the noti...

During mammalian brain development, neural progenitor cells undergo symmetric proliferative divisions followed by asymmetric neurogenic divisions. The division mode of these self-renewing progenitors, together with the cell fate of their progeny, plays critical roles in determining the number of neurons and, ultimately, the size of the adult brain. In the past decade, remarkable progress has be...