Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap

Area of Science:

• Neuroscience
• Developmental Biology
• Genomics

Background:

• Neocortical area formation is guided by a progenitor cell protomap.
• This protomap is believed to arise from spatial differences in progenitor cell identity at the transcriptional level.
• Extracellular signals are thought to pattern these progenitor cells.

Purpose of the Study:

• To systematically investigate the nature and composition of the neocortical progenitor cell protomap.
• To analyze spatial and temporal gene expression in neocortical progenitor cells.
• To elucidate the role of Fibroblast Growth Factor (Fgf) signaling in neocortical patterning.

Main Methods:

• Genomic analyses of spatial and temporal neocortical progenitor cell gene expression.
• In vivo global analysis of cortical gene expression in Fgfr1 mutant mice.
• In vitro confirmation of Mest as a transcriptional target of Fgf8 signaling.

Main Results:

• No evidence for progenitor cell domains or compartments was found; instead, rostrocaudal gradients of gene expression were observed across the neocortex.
• Fgfr1 mutant mice exhibited altered expression of candidate protomap elements.
• Mest was confirmed as a direct transcriptional target of Fgf8 signaling and plays a role in establishing patterned gene expression.

Conclusions:

• Neocortical progenitor cell organization is characterized by rostrocaudal gradients, not discrete domains.
• Fgf signaling, particularly Fgf8, is crucial for establishing the neocortical protomap.
• Mest acts as a negative regulator within the Fgf8-controlled patterning system, contributing to the establishment of patterned gene expression in the developing neocortex.