Reduced Layer 4 Neurogenesis of the Primary Somatosensory and Primary Visual Cortex in Mice with Sall1 Deficient Microglia
Microglia are the resident macrophages of the in the central nervous system (CNS) that emigrate into the brain until the formation of the blood-brain barrier, where they undergo maturation and differentiation. Microglia are known to be involved in formation and maintenance of neuronal circuits, repair after injury, and adult neurogenesis. However, little is known about the mechanisms of early microglia development and their effects on early neural cell development. Through gene expression profiling, the spalt-like transcription factor 1 (Sall1) gene has been identified as a signature microglial gene, as it is not expressed by other mononuclear phagocytes in the brain. Our lab recently found that Sall1 is essential for normal morphological and molecular maturation of developing microglia. Thus, Sall1 conditional knockout (cKO) mice can be used to test the requirement of normal microglia development in neural cell development. Using these mice, we are analyzing neurogenesis in the neocortex and synaptic pruning in the visual thalamus. In postnatal (P8) Primary Somatosensory (S1) and Primary Visual (V1) cortex, we found that there is a significant reduction in the number of layer 4 (L4) neurons (S1: p=0.007, n=11; V1: p=0.034, n=9). This suggests that normal microglial development is required for normal neuron production. To investigate the cellular mechanism for such a role in microglia, we are analyzing brains in which the neurons are birth-dated by 5-Ethynyl-2′-deoxyuridine (EdU). Additionally, we plan on analyzing other developmental stages to learn whether the impeded development mechanisms are embryonic or postnatal. Lastly, we are analyzing early postnatal visual thalamus, where retinogeniculate axons from the two eyes are segregated in an activity- and microglia-dependent manner, using Cholera toxin subunit B (CTB) injection. This will test the requirement of normal microglia development in the microglia’s contribution to synapse pruning.