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

Abstract

SUMMARY 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 gene expression programs, 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.

Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity

“…Similarly, we identified Cask as a CThPN-specific gene particularly enriched in CThPN located in deeper layer VI. CASK regulates synaptic function and neuronal development, binding to critical transcriptional controls such as TBR1 and CTIP1 (Hsueh 2006; Kuo et al, 2010), both expressed by CThPN and other subtypes (McKenna et al, 2011; Greig et al, 2016). Interestingly, Cask KO mice exhibit abnormalities in synaptic transmission, and increased neuronal death in the thalamus (Atasoy et al, 2007), strongly suggesting important function of Cask , and Cask -related controls, regulating development of synaptic function in specific CThPN subsets.…”

“…Interestingly, CTIP1 and CTIP2 ( C oup- T f I nteracting P rotein 1 and 2 ), and FOG2 have common structural domains, such as the amino terminal repressor domain, and the CCHH zinc fingers able to interact with COUP-TFs (Huggins et al, 2001; Lin, et al, 2004). Ctip1 is highly expressed by CThPN in sensory cortices, but only weakly expressed by CThPN in motor cortex (Greig et al, 2016). It is possible that CTIP1 regulates FOG2 interaction with COUP-TF1 in an area-specific manner, and/or compensates for Fog2 function in sensory areas.…”

Ctip1 Regulates the Balance between Specification of Distinct Projection Neuron Subtypes in Deep Cortical Layers

“…In contrast, Ctip1 overexpression in vivo represses Ctip2 expression and reduces the number of neurons projecting subcerebrally, while increasing the number of neurons projecting through the corpus callosum. In accompanying work, we report that Ctip1 controls the acquisition of sensory area identity and area-specific input/output connectivity (Greig et al, 2016), and thus serves to integrate the dual processes of subtype and area development in neocortex.…”

Building a lineage from single cells: genetic techniques for cell lineage tracking

“…A pulse of tamoxifen administration with an inducible Cre system can be used to determine lineage relationships 49 . Leakiness is a common problem of inducible Cre systems 50 but, nonetheless, these inducible systems have been used for lineage tracing in many adult tissues.…”