Role of DSCAM in the development of motor circuits

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Motor control results from the interplay between the brain and the spinal cord. The brain initiates, selects, and plans the appropriate motor program to match environmental constraints, while the spinal cord translates this descending command into motor actions. Critical to motor functions is the formation of neuronal networks in the brain and spinal cord, which depends highly on signaling pathways. Some of these signaling molecules are thought to guide growing axons to their proper targets, while others contribute to the cell positioning across the central nervous system. Using mouse genetics, it is now possible to alter gene expression by genetic deletion or overexpression in the mouse, thus allowing us to broaden and deepen our understanding of signaling molecules crucial to the development of motor circuits. My research program focuses on some of these signaling pathways, such as DSCAM (a cell adherence molecule associated to Down Syndrome). Recently, using mutant mice lacking DSCAM, we have shown that DSCAM is important to locomotor control and postural adjustments, it contributes to the normal development of the spinal locomotor and sensorimotor circuits, as well as the establishment of the motor cortex. My short-term objectives in the current program are to identify and characterize how DSCAM contributes to the formation of cortical, spinal, and sensory circuits important to motor control and locomotion. Using the CRE-LOX technology, we will manipulate DSCAM expression by overexpression or mutation in specific neuronal populations in order to investigate how DSCAM contributes anatomically, physiologically, and functionally to the establishment of supraspinal, spinal, and sensory circuits in the mouse. We will address the following aims:Aim 1: To study the contribution of DSCAM in the development of the motor cortex.Aim 2: To identify and characterize the role of DSCAM in the spinal locomotor circuit.Aim 3: To evaluate the role of DSCAM in the establishment of the spinal sensorimotor circuit.By the completion of the 5-year term of this research, we will have a better understanding of the role of cortical, spinal and sensory DSCAM, and their functional contribution to motor control and locomotion.