Ctip1 Controls Acquisition of Sensory Area Identity and Establishment of Sensory Input Fields in the Developing Neocortex

• Published in: Neuron (Cambridge, Mass.) Vol. 90; no. 2; pp. 261 - 277
• Main Authors: Greig, Luciano C., Woodworth, Mollie B., Greppi, Chloé, Macklis, Jeffrey D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.04.2016; Elsevier Limited
• Subjects: Acquisitions & mergers; Animals; Axons - physiology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Carrier Proteins - physiology; Cell Differentiation - genetics; Gene expression; Gene Expression Regulation, Developmental - genetics; Hybridization; Mice; Mice, Knockout; Mutation; Neocortex - cytology; Neocortex - growth & development; Neocortex - physiology; Nervous system; Neurons; Neurons - physiology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; Signal Transduction - physiology; Spinal cord; Studies; Thalamus - cytology; Thalamus - physiology; Transcription factors
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2016.03.008

While transcriptional controls over the size and relative position of cortical areas have been identified, less is known about regulators that direct acquisition of area-specific characteristics. Here, we report that the transcription factor Ctip1 functions in primary sensory areas to repress motor and activate sensory programs of gene expression, enabling establishment of sharp molecular boundaries defining functional areas. In Ctip1 mutants, abnormal gene expression leads to aberrantly motorized corticocortical and corticofugal output connectivity. Ctip1 critically regulates differentiation of layer IV neurons, and selective loss of Ctip1 in cortex deprives thalamocortical axons of their receptive “sensory field” in layer IV, which normally provides a tangentially and radially defined compartment of dedicated synaptic territory. Therefore, although thalamocortical axons invade appropriate cortical regions, they are unable to organize into properly configured sensory maps. Together, these data identify Ctip1 as a critical control over sensory area development. •Transcription factor Ctip1 is highly expressed in all primary sensory areas•Ctip1 directs acquisition of sensory area identity and represses motor area identity•Output connectivity of sensory areas is partially motorized in Ctip1 mutants•Ctip1 establishes “sensory fields” in layer IV, enabling sensory map formation Graded progenitor expression of transcriptional regulators determines the size and position of cortical areas. However, much less is known about the cortex-intrinsic mechanisms that control later stages of arealization. Greig et al. report that transcription factor Ctip1 drives sensory-specific differentiation, including gene expression, output connectivity, and formation of topographic maps.