Satb2 Is Required for the Development of a Spinal Exteroceptive Microcircuit that Modulates Limb Position

•ISRSatb2 neurons receive direct and indirect inputs from multiple sensory modalities•ISRSatb2 neurons synaptically target motor command layers of the ventral spinal cord•Satb2 regulates the connectivity of ISRSatb2 neurons•Satb2 mutant mice display abnormal joint flexion during specific motor behaviors

SummaryMotor behaviors such as walking or withdrawing the limb from a painful stimulus rely upon integrative multimodal sensory circuitry to generate appropriate muscle activation patterns. Both the cellular components and the molecular mechanisms that instruct the assembly of the spinal sensorimotor system are poorly understood. Here we characterize the connectivity pattern of a sub-population of lamina V inhibitory sensory relay neurons marked during development by the nuclear matrix and DNA binding factor Satb2 (ISRSatb2). ISRSatb2 neurons receive inputs from multiple streams of sensory information and relay their outputs to motor command layers of the spinal cord. Deletion of the Satb2 transcription factor from ISRSatb2 neurons perturbs their cellular position, molecular profile, and pre- and post-synaptic connectivity. These alterations are accompanied by abnormal limb hyperflexion responses to mechanical and thermal stimuli and during walking. Thus, Satb2 is a genetic determinant that mediates proper circuit development in a core sensory-to-motor spinal network.