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Stress often affects eating behaviors, increasing caloric intake in some individuals and decreasing it in others. The determinants of feeding responses to stress are unknown, in part because this issue is rarely studied in rodents. We focused our efforts on the novelty-suppressed feeding (NSF) assay, which uses latency to eat as readout of anxiety-like behavior, but rarely assesses feeding per se. We explored how key variables in experimental paradigms - estrous and diurnal cyclicity, age and duration of social isolation, prandial state, diet palatability, and elevated body weight - influence stress-induced anxiety-like behavior and food intake in male and female C57BL/6J mice. Latency to eat in the novel environment is increased in both sexes across most of the conditions tested, while effects on caloric intake are variable. In the common NSF assay (i.e., lean mice in the light cycle), sex-specific effects of the length of social isolation, and not estrous cyclicity, are the main source of variability. Under conditions that are more physiologically relevant for humans (i.e., overweight mice in the active phase), the novel stress now elicits robust hyperphagia in both sexes . This novel model of stress eating can be used to identify underlying neuroendocrine and neuronal substrates. Moreover, these studies can serve as a framework to integrate cross-disciplinary studies of anxiety and feeding related behaviors in rodents., Competing Interests: MF, IC, NS, CL, LZ No competing interests declared, (© 2022, Francois et al.)

Heterogeneous populations of hypothalamic neurons orchestrate energy balance via the release of specific signatures of neuropeptides. However, how specific intracellular machinery controls peptidergic identities and function of individual hypothalamic neurons remains largely unknown. The transcription factor T-box 3 (Tbx3) is expressed in hypothalamic neurons sensing and governing energy status, whereas human TBX3 haploinsufficiency has been linked with obesity. Here, we demonstrate that loss of Tbx3 function in hypothalamic neurons causes weight gain and other metabolic disturbances by disrupting both the peptidergic identity and plasticity of Pomc/Cart and Agrp/Npy neurons. These alterations are observed after loss of Tbx3 in both immature hypothalamic neurons and terminally differentiated mouse neurons. We further establish the importance of Tbx3 for body weight regulation in Drosophila melanogaster and show that TBX3 is implicated in the differentiation of human embryonic stem cells into hypothalamic Pomc neurons. Our data indicate that Tbx3 directs the terminal specification of neurons as functional components of the melanocortin system and is required for maintaining their peptidergic identity. In summary, we report the discovery of a key mechanistic process underlying the functional heterogeneity of hypothalamic neurons governing body weight and systemic metabolism.

Evidence of male-to-female sexual transmission of Zika virus (ZIKV) and viral RNA in semen and sperm months after infection supports a potential role for testicular cells in ZIKV propagation. Here, we demonstrate that germ cells (GCs) are most susceptible to ZIKV. We found that only GCs infected by ZIKV, but not those infected by dengue virus and yellow fever virus, produce high levels of infectious virus. This observation coincides with decreased expression of interferon-stimulated gene Ifi44l in ZIKV-infected GCs, and overexpression of Ifi44l results in reduced ZIKV production. Using primary human testicular tissue, we demonstrate that human GCs are also permissive for ZIKV infection and production. Finally, we identified berberine chloride as a potent inhibitor of ZIKV infection in both murine and human testes. Together, these studies identify a potential cellular source for propagation of ZIKV in testes and a candidate drug for preventing sexual transmission of ZIKV.

To address the expression and function of Hoxb13, the 5' most Hox gene in the HoxB cluster, we have generated mice with loss-of-function and beta-galactosidase reporter insertion alleles of this gene. Mice homozygous for Hoxb13 loss-of-function mutations show overgrowth in all major structures derived from the tail bud, including the developing secondary neural tube (SNT), the caudal spinal ganglia, and the caudal vertebrae. Using the beta-galactosidase reporter allele of Hoxb13, also a loss-of-function allele, we found that the expression patterns of Hoxb13 in the developing spinal cord and caudal mesoderm are closely associated with overgrowth phenotypes in the tails of homozygous mutant animals. These phenotypes can be explained by the observed increased cell proliferation and decreased levels of apoptosis within the tail of homozygous mutant mice. This analysis of Hoxb13 function suggests that this 5' Hox gene may act as an inhibitor of neuronal cell proliferation, an activator of apoptotic pathways in the SNT, and as a general repressor of growth in the caudal vertebrae., (Copyright 2003 Elsevier Science (USA))

The diencephalon comprises three functionally distinct regions: synencephalon, dorsal thalamus, and ventral thalamus. Patterning of the diencephalon has been proposed to involve subdivision of its anteroposterior axis into segments, neuromeres or prosomeres (Bergquist and Kallen, 1954; Vaage, 1969; Figdor and Stern, 1993; Rubenstein et al., 1994; Redies et al., 2000; Yoon et al., 2000). However, the number and sequence of diencephalic neuromeres, or even their existence, are uncertain. We have examined the proposed subdivisions by morphology, gene expression, acquisition of boundary-specific phenotypes, and cell lineage restriction. We find that at stage 16 in chick the diencephalon is divided into synencephalon and parencephalon. The synencephalon exhibits neuromeric morphology, expresses Prox, and acquires neuromere boundary properties at its interface with both the midbrain and the parencephalon. Although the mesencephalic/synencephalic boundary restricts cell mixing, the synencephalic/parencephalic boundary does not. Similarly, there is no lineage restriction between the parencephalon and the more rostral forebrain (secondary prosencephalon). Subdivision of the parencephalon into ventral and dorsal thalamus involves the formation of a narrow intraparencephalic territory, the zona limitans intrathalamica (zli). This is correlated with the acquisition of cell lineage restriction at both anterior and posterior borders of the zli, the appearance of boundary-specific properties, and Gbx2 and Dlx2 expression in dorsal thalamic and ventral thalamic territories, respectively. At stage 22, the synencephalon is divided into two domains, distinguished by differential gene expression and tissue morphology, but associated with neither a boundary phenotype nor cell lineage restriction. Our results suggest that the diencephalon does not have an overt segmental pattern.