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The article discusses a study conducted by P. Bi and colleagues on the multiple roles played by Notch signalling in the regulation of adipose browning and energy homeostasis in mammals. It mentions the deletion of gene encoding the Notch 1 receptor or the gene encoding the Notch signaling pathway primary transcriptional effector by the authors to assess the direct relationship between Notch signaling levels and brown adipose tissue (BAT).

Background: Members of the Snail gene family, which encode zinc finger proteins that function as transcriptional repressors, play essential roles during embryonic development in vertebrates. Mouse embryos with conditional deletion of the Snail1 (Snai1) gene in the epiblast, but not in most extraembryonic membranes, exhibit defects in left-right asymmetry specification and migration of mesoderm cells through the posterior primitive streak. Here we describe phenotypic defects that result in death of the mutant embryos by 9.5 days of gestation. Findings: Endothelial cells differentiated in epiblast-specific Snai1-deficient embryos, but formation of an interconnected vascular network was abnormal. To determine whether the observed vascular defects were dependent on disruption of blood flow, we analyzed vascular remodeling in cultured allantois explants from the mutant embryos. Similar vascular defects were observed in the mutant allantois explants. Conclusion: These studies demonstrate that lethality in the Snai1-conditional mutant embryos is caused by multiple defects in the cardiovascular system. [ABSTRACT FROM AUTHOR]

Conclusion: Jagged1-mediated Notch signaling regulates hair cell (HC) production in a distinct way rather than lateral inhibition mediated by Hes1 and Hes5. Jagged1 may interact with Notch3, probably via candidate downstream mediators Hesr1 and Hesr2, regulating the prosensory formation in the early stage. Objectives: To explore the function of the Jagged1-mediated Notch signaling pathway in mammalian inner ear development and its possible mechanism. Methods: Using conditional gene targeting, a novel Jagged1 conditional knockout (Jag1-cko), Pax8cre/+; Jag1flox/flox, was established. The auditory brainstem response and swim ability test were utilized to identify functional disability. The expression of Jagged1, Notch3, Hes1, Hesr1, and Hesr2 was detected by immunofluorescence and immunohistochemistry. Results: Our Jag1-cko model was established and survived well. It presented hearing impairment and balance disturbance with 'waltzing' behavior. Cochleae and vestibular apparatus were all found in our Jag1-cko model. Patch deficiency of outer hair cells (OHCs) was found on the apical and middle turns of the auditory epithelium. OHCs were totally missing on the basal turn. The stereociliary bundles were disorientated on the cristae. Unlike Hes1, no expression of Notch3, Hesr1, and Hesr2 was found on embryonic day 13.5 of the Jag1-cko model. [ABSTRACT FROM AUTHOR]

Generation of effective immune responses requires expansion of rare antigen-specific CD4+ T cells. The magnitude of the responding population is ultimately determined by proliferation and survival. Both processes are tightly controlled to limit responses to innocuous antigens. Sustained expansion occurs only when innate immune sensors are activated by microbial stimuli or by adjuvants, which has important implications for vaccination. The molecular identity of the signals controlling sustained T-cell responses is not fully clear. Here, we describe a prominent role for the Notch pathway in this process. Coactivation of Notch allows accumulation of far greater numbers of activated CD4+ T cells than stimulation via T-cell receptor and classic costimulation alone. Notch does not overtly affect cell cycle entry or progression of CD4+ T cells. Instead, Notch protects activated CD4+ T cells against apoptosis after an initial phase of clonal expansion. Notch induces a broad antiapoptotic gene expression program that protects against intrinsic, as well as extrinsic, apoptosis pathways. Both Notch 1 and Notch2 receptors and the canonical effector RBPJ (recombination signal binding protein for immunoglobulin kappa J region) are involved in this process. Correspondingly, CD4+ T-cell responses to immunization with protein antigen are strongly reduced in mice lacking these components of the Notch pathway. Our findings, therefore, show that Notch controls the magnitude of CD4+ T-cell responses by promoting cellular longevity. [ABSTRACT FROM AUTHOR]

Palate development requires precise regulation of gene expression changes, morphogenetic movements and alterations in cell physiology. Defects in any of these processes can result in cleft palate, a common human birth defect. The Snail gene family encodes transcriptional repressors that play essential roles in the growth and patterning of vertebrate embryos. Here we report the functions of Snail (Snai1) and Slug (Snai2) genes during palate development in mice. Snai2-/- mice exhibit cleft palate, which is completely penetrant on a Snai1 heterozygous genetic background. Cleft palate in Snai1+/- Snai2-/- embryos is due to a failure of the elevated palatal shelves to fuse. Furthermore, while tissue-specific deletion of the Snai1 gene in neural crest cells does not cause any obvious defects, neural-crest-specific Snai1 deletion on a Snai2-/- genetic background results in multiple craniofacial defects, including a cleft palate phenotype distinct from that observed in Snai1+/- Snai2-/- embryos. In embryos with neural-crest-specific Snai1 deletion on a Snai2-/- background, palatal clefting results from a failure of Meckel's cartilage to extend the mandible and thereby allow the palatal shelves to elevate, defects similar to those seen in the Pierre Robin Sequence in humans. [ABSTRACT FROM AUTHOR]

Summary: CD4+ T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4+ T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch. [Copyright &y& Elsevier]

Investigates the role of Notch signaling pathway in the establishment of left-right asymmetry in mice. Regulation of Nodal gene expression; Physiology of the Notch signaling pathway; Presence of Nodal cilia in DII1 mutant embryos; Significance of Nodal gene expression to the determination of left-right axis.