Precise pattern of recombination in serotonergic and hypothalamic neurons in a Pdx1-cre transgenic mouse line
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Background: Multicellular organisms are characterized by a remarkable diversity of morphologically distinct and functionally specialized cell types. Transgenic techniques for the manipulation of gene expression in specific cellular populations are highly useful for elucidating the development and function of these cellular populations. Given notable similarities in developmental gene expression between pancreatic beta cells and serotonergic neurons, we examined the pattern of Cre-mediated recombination in the nervous system of a widely used mouse line, Pdx1-cre (formal designation, Tg(Ipf1-cre)89.1Dam), in which the expression of Cre recombinase is driven by regulatory elements upstream of the pdx1 (pancreatic-duodenal homeobox 1) gene. Methods: Single (hemizygous) transgenic mice of the pdx1-cre(Cre/0) genotype were bred to single (hemizygous) transgenic reporter mice (Z/EG and rosa26R lines). Recombination pattern was examined in offspring using whole-mount and sectioned histological preparations at e9.5, e10.5, e11.5, e16.5 and adult developmental stages. Results: In addition to the previously reported pancreatic recombination, recombination in the developing nervous system and inner ear formation was observed. In the central nervous system, we observed a highly specific pattern of recombination in neuronal progenitors in the ventral brainstem and diencephalon. In the rostral brainstem (r1-r2), recombination occurred in newborn serotonergic neurons. In the caudal brainstem, recombination occurred in non-serotonergic cells. In the adult, this resulted in reporter expression in the vast majority of forebrain-projecting serotonergic neurons (located in the dorsal and median raphe nuclei) but in none of the spinal cord-projecting serotonergic neurons of the caudal raphe nuclei. In the adult caudal brainstem, reporter expression was widespread in the inferior olive nucleus. In the adult hypothalamus, recombination was observed in the arcuate nucleus and dorsomedial hypothalamus. Recombination was not observed in any other region of the central nervous system. Neuronal expression of endogenous pdx1 was not observed. Conclusions: The Pdx1-cre mouse line, and the regulatory elements contained in the corresponding transgene, could be a valuable tool for targeted genetic manipulation of developing forebrain-projecting serotonergic neurons and several other unique neuronal sub-populations. These results suggest that investigators employing this mouse line for studies of pancreatic function should consider the possible contributions of central nervous system effects towards resulting phenotypes.
transcription factor idx1/ipf1
medicine, research & experimental
Published Version (Please cite this version)10.1186/1423-0127-17-82
CitationHonig,Gerard;Liou,Angela;Berger,Miles;German,Michael S.;Tecott,Laurence H.. 2010. Precise pattern of recombination in serotonergic and hypothalamic neurons in a Pdx1-cre transgenic mouse line. Journal of Biomedical Science 17( ): 82-82.
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Associate Professor of Anesthesiology
My research team focuses on understanding the cause of postoperative cognitive dysfunction (POCD) and delirium, and whether these disorders are caused by perioperative changes in Alzheimer's disease pathways. We are also interested in whether delirium or POCD are associated with an increased long term risk of developing Alzheimer's disease. Towards these ends, we use a combination of methods including cognitive testing, CSF and blood sampling, functional neuroimaging, and rigorous biochemical as