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The cochlear nuclear complex (CN) is the entry point for central auditory processing. Although constituent neurons have been studied physiologically, their embryological origins and molecular profiles remain obscure. Applying intersectional and subtractive genetic fate mapping approaches, we show that this complex develops modularly from genetically(More)
Central serotonin-producing neurons are heterogeneous-differing in location, morphology, neurotoxin sensitivity and associated clinical disorders-but the underpinnings of this heterogeneity are largely unknown, as are the markers that distinguish physiological subtypes of serotonergic neurons. Here we redefined serotonergic subtypes on the basis of genetic(More)
The lower rhombic lip (LRL) is a germinal zone in the dorsal hindbrain productive of tangentially migrating neurons, streaming extramurally (mossy fiber neurons) or intramurally (climbing fiber neurons). Here we show that LRL territory, operationally defined by Wnt1 expression, is parceled into molecular subdomains predictive of cell fate. Progressing(More)
Human infertility and recurrent pregnancy loss caused by implantation defects are poorly understood. Hoxa-10-deficient female mice have severe infertility and recurrent pregnancy loss due to defective uterine implantation. Gene expression profiling experiments reveal that Hoxa-10 is an important regulator of two critical events in implantation: stromal cell(More)
Small cell lung carcinoma (SCLC) is a highly lethal, smoking-associated cancer with few known targetable genetic alterations. Using genome sequencing, we characterized the somatic evolution of a genetically engineered mouse model (GEMM) of SCLC initiated by loss of Trp53 and Rb1. We identified alterations in DNA copy number and complex genomic(More)
The possible role of a non-specific cell-mediated immune reaction in the pathogenesis of Parkinson's disease (PD) is discussed. It was found that the killer cell activity of PD patients below 60 years of age was significantly lower than in the older age groups or in the age-matched control group. On the other hand, it was also found that the killer cell(More)
BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263(More)
INTRODUCTION Chromosomal rearrangements involving neurotrophic tyrosine kinase 1 (NTRK1) occur in a subset of non-small cell lung cancers (NSCLCs) and other solid tumor malignancies, leading to expression of an oncogenic TrkA fusion protein. Entrectinib (RXDX-101) is an orally available tyrosine kinase inhibitor, including TrkA. We sought to determine the(More)
BACKGROUND Mammary analogue secretory carcinoma (MASC) is a recently described pathologic entity. We report the case of a patient with an initial diagnosis of salivary acinic cell carcinoma later reclassified as MASC after next-generation sequencing revealed an ETV6-NTRK3 fusion. PATIENTS AND METHODS This alteration was targeted with the pan-Trk inhibitor(More)