FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2137265280> ?p ?o ?g. }

• W2137265280 endingPage "5827" @default.
• W2137265280 startingPage "5805" @default.
• W2137265280 abstract "Many genes involved in brain development have been associated with human neurodevelopmental disorders, but underlying pathophysiological mechanisms remain undefined. Human genetic and mouse behavioral analyses suggest that ENGRAILED-2 (EN2) contributes to neurodevelopmental disorders, especially autism spectrum disorder. In mouse, En2 exhibits dynamic spatiotemporal expression in embryonic mid-hindbrain regions where monoamine neurons emerge. Considering their importance in neuropsychiatric disorders, we characterized monoamine systems in relation to forebrain neurogenesis in En2-knockout (En2-KO) mice. Transmitter levels of serotonin, dopamine and norepinephrine (NE) were dysregulated from Postnatal day 7 (P7) to P21 in En2-KO, though NE exhibited the greatest abnormalities. While NE levels were reduced ∼35% in forebrain, they were increased 40 -: 75% in hindbrain and cerebellum, and these patterns paralleled changes in locus coeruleus (LC) fiber innervation, respectively. Although En2 promoter was active in Embryonic day 14.5 -: 15.5 LC neurons, expression diminished thereafter and gene deletion did not alter brainstem NE neuron numbers. Significantly, in parallel with reduced NE levels, En2-KO forebrain regions exhibited reduced growth, particularly hippocampus, where P21 dentate gyrus granule neurons were decreased 16%, suggesting abnormal neurogenesis. Indeed, hippocampal neurogenic regions showed increased cell death (+77%) and unexpectedly, increased proliferation. Excess proliferation was restricted to early Sox2/Tbr2 progenitors whereas increased apoptosis occurred in differentiating (Dcx) neuroblasts, accompanied by reduced newborn neuron survival. Abnormal neurogenesis may reflect NE deficits because intra-hippocampal injections of β-adrenergic agonists reversed cell death. These studies suggest that disruption of hindbrain patterning genes can alter monoamine system development and thereby produce forebrain defects that are relevant to human neurodevelopmental disorders." @default.
• W2137265280 created "2016-06-24" @default.
• W2137265280 creator A5007362000 @default.
• W2137265280 creator A5012289692 @default.
• W2137265280 creator A5013023255 @default.
• W2137265280 creator A5015234262 @default.
• W2137265280 creator A5021439333 @default.
• W2137265280 creator A5048411184 @default.
• W2137265280 creator A5050268402 @default.
• W2137265280 creator A5052166790 @default.
• W2137265280 creator A5054343981 @default.
• W2137265280 creator A5055976283 @default.
• W2137265280 creator A5059818341 @default.
• W2137265280 creator A5063501456 @default.
• W2137265280 creator A5068347013 @default.
• W2137265280 creator A5077746312 @default.
• W2137265280 date "2015-07-28" @default.
• W2137265280 modified "2023-10-15" @default.
• W2137265280 title "<i>Engrailed-2</i>(<i>En2</i>) deletion produces multiple neurodevelopmental defects in monoamine systems, forebrain structures and neurogenesis and behavior" @default.
• W2137265280 cites W1761987582 @default.
• W2137265280 cites W1815206142 @default.
• W2137265280 cites W1837201888 @default.
• W2137265280 cites W1913938270 @default.
• W2137265280 cites W1923414836 @default.
• W2137265280 cites W1964980012 @default.
• W2137265280 cites W1966988500 @default.
• W2137265280 cites W1967276946 @default.
• W2137265280 cites W1969469789 @default.
• W2137265280 cites W1972354147 @default.
• W2137265280 cites W1972622243 @default.
• W2137265280 cites W1977592638 @default.
• W2137265280 cites W1979420039 @default.
• W2137265280 cites W1979453856 @default.
• W2137265280 cites W1980042496 @default.
• W2137265280 cites W1981201311 @default.
• W2137265280 cites W1982643896 @default.
• W2137265280 cites W1983548799 @default.
• W2137265280 cites W1984769882 @default.
• W2137265280 cites W1985713454 @default.
• W2137265280 cites W1986624226 @default.
• W2137265280 cites W1987092198 @default.
• W2137265280 cites W1991009413 @default.
• W2137265280 cites W1992036758 @default.
• W2137265280 cites W1994345197 @default.
• W2137265280 cites W1994348124 @default.
• W2137265280 cites W1997338117 @default.
• W2137265280 cites W1998793497 @default.
• W2137265280 cites W1999299319 @default.
• W2137265280 cites W2002012536 @default.
• W2137265280 cites W2002869948 @default.
• W2137265280 cites W2003627673 @default.
• W2137265280 cites W2007746109 @default.
• W2137265280 cites W2011828358 @default.
• W2137265280 cites W2011911237 @default.
• W2137265280 cites W2012664976 @default.
• W2137265280 cites W2014099101 @default.
• W2137265280 cites W2014711343 @default.
• W2137265280 cites W2017826413 @default.
• W2137265280 cites W2018911570 @default.
• W2137265280 cites W2018945144 @default.
• W2137265280 cites W2019317402 @default.
• W2137265280 cites W2020777374 @default.
• W2137265280 cites W2020933530 @default.
• W2137265280 cites W2022386867 @default.
• W2137265280 cites W2023675343 @default.
• W2137265280 cites W2026670155 @default.
• W2137265280 cites W2027312665 @default.
• W2137265280 cites W2027904526 @default.
• W2137265280 cites W2029086126 @default.
• W2137265280 cites W2030325164 @default.
• W2137265280 cites W2030887667 @default.
• W2137265280 cites W2032813157 @default.
• W2137265280 cites W2033065184 @default.
• W2137265280 cites W2034104365 @default.
• W2137265280 cites W2035900692 @default.
• W2137265280 cites W2037302793 @default.
• W2137265280 cites W2037457092 @default.
• W2137265280 cites W2037516419 @default.
• W2137265280 cites W2039226995 @default.
• W2137265280 cites W2040268226 @default.
• W2137265280 cites W2043659972 @default.
• W2137265280 cites W2045283840 @default.
• W2137265280 cites W2046683077 @default.
• W2137265280 cites W2048650676 @default.
• W2137265280 cites W2053806499 @default.
• W2137265280 cites W2053972908 @default.
• W2137265280 cites W2054244592 @default.
• W2137265280 cites W2057516812 @default.
• W2137265280 cites W2057594895 @default.
• W2137265280 cites W2062636482 @default.
• W2137265280 cites W2063411716 @default.
• W2137265280 cites W2063679642 @default.
• W2137265280 cites W2063976611 @default.
• W2137265280 cites W2064798943 @default.
• W2137265280 cites W2065019245 @default.
• W2137265280 cites W2066477949 @default.
• W2137265280 cites W2069194632 @default.
• W2137265280 cites W2069860218 @default.

• next