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A V Chan

Publications and source records attributed to A V Chan.

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Signaling pathways that regulate specification of neurons in developing cerebral cortex.

The expression of the limbic system-associated membrane protein (LAMP), a marker of specific functional regions of the cerebral cortex, has been used to determine the environmental signals that regulate cortical regionalization. Transplant and cell culture studies have shown previously that the fate of precursor cells, based on LAMP expression, is amenable to regulation by exposure to novel environmental stimuli. This has been demonstrated in vitro to be dependent upon exposure to transforming factor-alpha and collagen type IV. Results following exposure to the inductive signals for a specific duration indicate a cell cycle dependence on the decision to become a limbic or nonlimbic cortical neuron. It appears, therefore, that areal and laminar fates are both influenced by mechanisms that specify commitment early in cortical development.

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Mechanisms specifying area fate in cortex include cell-cycle-dependent decisions and the capacity of progenitors to express phenotype memory.

Progenitor cells in the early developing cerebral cortex produce neurons destined for discrete functional areas in response to specific inductive signals. Using lineage analysis, we show that cortical progenitor cells at different fetal ages retain the memory of an area-specific inductive signal received in vivo, even though they may pass through as many as two cell cycles in the absence of the signal in culture. When exposed to inductive signals in vitro, only those progenitors that progress through at least one complete cell cycle alter their areal phenotype. Our findings suggest that induction of an areal phenotype is linealy inherited, with the phenotype specified prior to the final cell cycle.

Animals↗