Rostral-caudal distribution of Emx1-lineage stem/transit amplifying cells and lineage progression in embryonic cortex depend on Hedgehog signaling.

Lineage progression of neural precursors to an EGF-responsive state can be promoted by several extrinsic signals, including fibroblast growth factor 2 (FGF2) and Hedgehog (Hh). It has been suggested that EGF-responsive precursors in the embryonic cerebral cortex originate in the ventral telencephalon in an FGF-dependent manner and migrate dorsally. To determine whether cortical EGF-responsive cells originate locally from dorsal precursors, we marked these precursors using Emx1-cre and the cre reporter Z/EG and observed a local origin for EGF-responsive cells.

Akt1 interacts with epidermal growth factor receptors and hedgehog signaling to increase stem/transit amplifying cells in the embryonic mouse cortex.

A subset of precursors in the embryonic mouse cortex and in neurospheres expresses a higher level of the serine/threonine kinase Akt1 than neighboring precursors. We reported previously that the functional significance of high Akt1 expression was enhanced Akt1 activity, resulting in an increase in survival, proliferation, and self-renewal of multipotent stem/transit amplifying cells. Akt1 can interact with a number of signaling pathways, but the extrinsic factors that are required for specific effects of elevated Akt1 expression have not been identified.

Environmental signals elicit multiple responses in dorsal telencephalic progenitors by threshold-dependent mechanisms.

Environmental signals including epidermal growth factor family members, Shh, fibroblast growth factor, and bone morphogenetic protein (BMP) can affect multiple processes during the development of the central nervous system, raising questions about the mechanisms that determine how these pleiotropic signals are interpreted to elicit appropriate responses at specific times and locations. Here we address the idea that different thresholds of stimulation determine how progenitors in the dorsal telencephalon interpret these signals. One mechanism for achieving different thresholds of signaling is illustrated by the developmental increase in the level of epidermal growth factor receptor (EGFR) expression among a subset of progenitors in the late embryonic telencephalon.

Attraction or repulsion: a matter of individual taste?

Cell migration along the correct paths is critical to normal organogenesis and tissue repair, and goes awry in tumor dissemination. Understanding the molecular cues that control such migration would provide opportunities to control these events. Recent findings in Drosophila highlight the role of the epidermal growth factor receptor (EGFR) in chemotaxis and pathfinding during development.

Akt-1 expression level regulates CNS precursors.

Although most cells in the embryonic mouse cortex express the serine-threonine kinase Akt-1, a small population of progenitors expresses Akt-1 protein at a higher level. To determine the functional significance of this difference, we used a retrovirus to increase Akt-1 expression in cortical progenitors. Increased Akt expression enhanced Akt activation after growth factor stimulation of progenitors.