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The transforming growth factor beta (TGFβ) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFβ signals. Here, we show that Smad3 is an insensitive TGFβ transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFβ signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFβ signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFβ/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity and differential transcriptional activity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFβ signaling and have distinct roles in regulating early developmental events.

In this paper we report the structural, electrical and optical properties of epitaxial Ba(Sb x Sn1−x )O3 (x = 0–0.30) (BSSO) films grown on SrTiO3(0 0 1) substrates by the pulsed laser deposition method. The investigation reveals that the transport and optical characteristics of BSSO films depend very sensitively on the Sb-doping content. Temperature-dependent resistivity measurements show that at low Sb contents (x = 0.03, 0.07) the metal–semiconductor transition occurs at 150 K and 80 K, respectively, and the semiconductor behaviour appears in high doped (x = 0.15, 0.30) films. The transmittance decreases significantly from about 80% to nearly zero in the visible region and the optical band gap shifts from 3.48 to 4.0 eV with increasing Sb content in the films. The lowest room-temperature resistivity of 2.43 mΩ cm with carrier density and mobility of 1.65 × 1021 cm−3 and 1.75 cm2 V−1 s−1 was obtained in the films with doping at x = 0.07. By employing them as bottom electrodes we have fabricated transparent Pb(Zr0.52Ti0.48)O3 ferroelectric capacitors showing square polarization–electric field hysteresis loops, indicating that these perovskite-type BSSO films at low doping can be potentially used in transparent devices especially based on all-perovskite heterostructures.

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The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh-driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.

Articles you may be interested inDopant-site-dependent scattering by dislocations in epitaxial films of perovskite semiconductor BaSnO3 APL Mat. 2, 056107 (2014); 10.1063/1.4874895 Infrared-optical spectroscopy of transparent conducting perovskite (La,Ba)SnO3 thin films Appl. Phys. Lett.