ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis

Cardiogenesis requires the orchestrated spatiotemporal tuning of BMP signalling upon the balance between induction and counter-acting suppression of the differentiation of the cardiac tissue. SMADs are key intracellular transducers and the selective degradation of SMADs by the ubiquitin–proteasome system is pivotal in the spatiotemporal tuning of BMP signalling. However, among three SMADs for BMP signalling, SMAD1/5/9, only the specific E3 ligase of SMAD9 remains poorly investigated. Here, we report for the first time that SMAD9, but not the other SMADs, is ubiquitylated by the E3 ligase ASB2 and targeted for proteasomal degradation. ASB2, as well as Smad9, is conserved among vertebrates. ASB2 expression was specific to the cardiac region from the very early stage of cardiac differentiation in embryogenesis of mouse. Knockdown of Asb2 in zebrafish resulted in a thinned ventricular wall and dilated ventricle, which were rescued by simultaneous knockdown of Smad9. Abundant Smad9 protein leads to dysregulated cardiac differentiation through a mechanism involving Tbx2, and the BMP signal conducted by Smad9 was downregulated under quantitative suppression of Smad9 by Asb2. Our findings demonstrate that ASB2 is the E3 ligase of SMAD9 and plays a pivotal role in cardiogenesis through regulating BMP signalling.

Cellular organization of visual information processing channels in the mouse visual cortex

Visual processing and behavior depend on specialized neural representations and information channels that encode distinct visual information and enable distinct computations. Our understanding of the neural substrate, however, remain severely limited by sparse recordings and the restricted range of visual areas and visual stimuli considered. We characterized in the mouse the multidimensional spatiotemporal tuning properties of > 30,000 layer 2/3 pyramidal neurons across seven areas of the cortex. The dataset reveals population specialized for processing of oriented and non-oriented contrast, spatiotemporal frequency, and motion speed. Areal analysis reveals profound functional diversity and specificity as well as highly specific representations of visual processing channels in distinct visual areas. Clustering analysis shows a branching of visual representations along the posterior to anterior axis, and between lateral and dorsal areas. Overall, this dataset provides a cellular-resolution atlas for understanding organizing principles underlying sensory representations across the cortex.SummaryVisual representations and visual channels are the cornerstones of mammalian visual processing and critical for a range of life sustaining behaviors. However, the lack of data sets spanning multiple visual areas preclude unambiguous identification of visual processing streams and the sparse, singular recording data sets obtained thus far are insufficient to reveal the functional diversity of visual areas and to study visual information channels. We characterized the tunings of over 30,000 cortical excitatory neurons from 7 visual areas to a broad array of stimuli and studied their responses in terms of their ability to encode orientation, spatiotemporal contrast and visual motion speed. We found all mouse visual cortical areas convey diverse information but show distinct biases in terms of numbers of neurons tuned to particular spatiotemporal features. Neurons in visual areas differ in their spatiotemporal tuning but also in their relative response to oriented and unoriented contrast. We uncovered a population that preferentially responds to unoriented contrast and shows only weak responses to oriented stimuli. This population is strongly overrepresented in certain areas (V1, LM and LI) and underrepresented in others (AL, RL, AM, and PM). Spatiotemporal tunings are broadly distributed in all visual areas indicating that all areas have access to broad spatiotemporal information. However, individual areas show specific biases. While V1 is heavily biased in favor of low spatial and temporal frequencies, area LM responds more strongly to mid-range frequencies. Areas PM and LI are biased in favor of slowly-varying high-resolution signals. By comparison, anterior areas AL, RL and AM are heavily biased in favor of fast-varying, low to mid spatial frequency signals. Critically, theses biases express themselves in vastly different number of cells tuned to particular features, suggesting differential sampling of visual processing channels across areas. Comparing across areas, we found divergent visual representations between anterior and posterior areas, and between lateral and dorsal areas, suggesting the segregated organization of cortical streams for distinct information processing.

Spatiotemporal Frequency Tuning Dynamics of Neurons in the Owl Visual Wulst

The transformation of spatial (SF) and temporal frequency (TF) tuning functions from broad-band/low-pass to narrow band-pass profiles is one of the key emergent properties of neurons in the mammalian primary visual cortex (V1). The mechanisms underlying such transformation are still a matter of ongoing debate. With the aim of providing comparative insights into the issue, we analyzed various aspects of the spatiotemporal tuning dynamics of neurons in the visual wulst of four awake owls. The wulst is the avian telencephalic target of the retinothalamofugal pathway and, in owls, bears striking functional analogy with V1. Most neurons in our sample exhibited fast and large-magnitude adaptation to the visual stimuli with response latencies very similar to those reported for V1. Moreover, latency increased as a function of stimulus SF but not TF, which suggests that parvo- and magno-like geniculate inputs could be converging onto single wulst neurons. No net shifts in preferred SF or TF were observed along the initial second of stimulation, but bandwidth decreased roughly during the first 200 ms after response latency for both stimulus dimensions. For SF, this occurred exclusively as a consequence of low-frequency suppression, whereas suppression was observed both at the low- and high-frequency limbs of TF tuning curves. Overall these results indicate that SF and TF tuning curves in the wulst are shaped by both feedforward and intratelencephalic suppressive mechanisms, similarly to what seems to be the case in the mammalian striate cortex.