Satb2 Is Required for Dendritic Arborization and Soma Spacing in Mouse Cerebral Cortex

Abstract

Self-avoidance is a mechanism by which dendrites from the same neuron repel one another in order to establish uniform coverage of the dendritic field. The importance of self-avoidance for the development of complex arborization patterns has been highlighted by studies of Drosophila sensory and mouse retinal neurons. However, it is unclear whether branch patterning in the mammalian central nervous system is also governed by this strategy. We reduced Satb2 expression in a population of layer II/III pyramidal neurons in vivo by RNA interference and found that the somas of Satb2-deficient neurons clumped together, and their dendrites failed to expand laterally but instead formed fascicles. Furthermore, experiments showed that reducing Satb2 caused the adhesion of not only neighboring Satb2-deficient neurons but also neighboring wild-type neurons. Our results indicate a cell autonomous and non-cell autonomous role for Satb2 in regulating the adhesive and/or repulsive properties of cerebral pyramidal neurons.

Transcriptional co-regulation of neuronal migration and laminar identity in the neocortex

“…3E), failing to enter the CP Britanova et al, 2008). Surprisingly, this neuronal migration defect is corrected within the first postnatal week, as most late-born neurons lacking Satb2 eventually reach their normal positions in the upper layers (Britanova et al, 2008;Zhang et al, 2011), indicating that the migration of upper layer neurons is not altogether defective, but is delayed in the absence of Satb2. The mechanisms that regulate the timing of the arrival of neurons to their proper CP location are unknown.…”

“…Consistent with these changes in molecular identity, corticocortical projection neurons in the absence of Satb2 misroute their axons to subcortical targets, leading to agenesis of the corpus callosum Britanova et al, 2008). Recently, Satb2 has also been shown to control the dendritic arborization of upper layer neurons (Zhang et al, 2011), indicating a broader role during neocortical development.The role of Satb2 in neuronal migration, similar to its role in the control of neuronal identity and projections, is layer dependent. In Satb2-deficient mice, early-born neurons migrate normally to the SP and deep cortical layers.…”

“…For example, the apical dendrites of both upper and deep layer neurons exhibit arborization near the MZ and are decorated by spines. In upper layer neurons, however, the upper layer-specific cut-like homeobox proteins CUX1 and CUX2 (Cubelos et al, 2010) regulate spine morphology and synaptogenesis, whereas SATB2 controls dendritic arborization (Zhang et al, 2011). The absence of these factors from the deep layers suggests that dendrite development and spine formation in deep-layer neurons are controlled by distinct, CUX-and SATB2-independent mechanisms, further supporting the notion that shared developmental processes might be transcriptionally driven in a layer-dependent manner.…”

Transcriptional Dysregulation of Neocortical Circuit Assembly in ASD

“…These defects in the Satb2 -deficient neocortex, therefore, are consistent with the potential contribution of SATB2 to ASD-relevant neural circuits. In addition, Satb2 controls the dendritic arborization and soma density of upper-layer neurons (Zhang et al, 2011), which may further contribute to the overall development of input and output connections in intracortical circuits. This role of Satb2 is also consistent with the disruption of dendritic spine morphology in ASD (Comery et al, 1997; Hutsler and Zhang, 2010; Irwin et al, 2000).…”

“…In contrast, a significant proportion of late-born neurons destined for the upper layers are stalled in the IZ, being unable to enter the CP (Alcamo et al, 2008; Britanova et al, 2008). This neuronal migration defect, however, was restricted to the perinatal ages, as these defects are corrected within the first post-natal week, with the majority of late-born neurons eventually arriving at their normal upper layer positions (Britanova et al, 2008; Zhang et al, 2011). These data suggest that, in the absence of Satb2 , neuronal migration is not altogether defective, but rather, delayed.…”