Precise pattern of recombination in serotonergic and hypothalamic neurons in a Pdx1-cre transgenic mouse line
Abstract
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.
Type
Other articleSubject
pancreatic epithelial-cellstranscription factor idx1/ipf1
beta-cells
neural cells
in-vitro
differentiation
expression
pcr
endocrine
mice
medicine, research & experimental
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http://hdl.handle.net/10161/4331Published Version (Please cite this version)
10.1186/1423-0127-17-82Citation
Honig,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.Collections
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Show full item recordScholars@Duke
Miles Berger
Assistant 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

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