The node, or its zebrafish equivalent, Kupffers Vesicle (KV), is thought to generate laterality cues through cilia‐dependent signaling. An interaction between Nodal ligands and Nodal antagonists around the node/KV is also required. Here we investigate whether loss of Brachyury/Notail or Tbx16/Spadetail disrupts the balance of Nodal ligands (Southpaw) and antagonists (Charon) around Kupffers Vesicle. Reduction of Spadetail or Notail disrupts expression of southpaw in the perinodal domains flanking Kupffers Vesicle. Similar to what was published for Notail, we find Spadetail is also required for expression of charon. We present evidence for the model that Notail has a direct role in regulating the charon promoter. In particular, a flanking genomic region with putative Notail binding sites can drive KV expression of a reporter in a Notail‐dependent fashion. This region also contains motifs for CSL/RBP‐J/Su(H). Consistent with this, we find charon expression is strongly Notch‐dependent whereas perinodal southpaw expression is not. Developmental Dynamics 236:2131–2146, 2007.

Adipocytes can be infected by SARS-CoV-2, potentially contributing to the obesity-associated severity of COVID-19. Circumstantial evidence points to angiotensin-converting enzyme 2 (ACE2) as the necessary receptor for adipocyte infection, but this has not been demonstrated experimentally. Using differentiated immortalized human preadipocyte lines that we developed, we found that visceral adipocytes express higher levels of ACE2 and are more susceptible to SARS-CoV-2 spike (S)-mediated luciferase-VSV infection than subcutaneous adipocytes. Overexpression of ACE2 significantly increased infection, whereas knockout of ACE2 significantly decreased S-mediated infection. Visceral adipocytes at baseline were susceptible to infection by SARS-CoV-2 (Delta variant); however, increased levels of viral transcript with time were not apparent. ACE2 knockout significantly decreased the susceptibility of visceral adipocytes to SARS-CoV-2, whereas overexpression of ACE2 resulted in increased SARS-CoV-2 infection and was associated with increased viral transcript levels with time, as well as induction of IL6, a marker of the proinflammatory response. Our results demonstrate that ACE2 confers susceptibility to SARS-CoV-2 infection of visceral adipocytes. Higher levels of ACE2 in these cells may play a role in establishment of infection and a proinflammatory response, potentially leading to pathogenesis.