title: Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis.
abstract: The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of COUP-TFI mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.|Institute of Genetics and Biophysics, CNR, Naples, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: Flore
authors.affiliation: Institute of Genetics and Biophysics, CNR, Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Ruberto
authors.affiliation: Institute of Biology Valrose, iBV, UMR INSERM1091/CNRS7277/UNS, 06108 Nice, France.|University of Nice Sophia Antipolis (UNS), Nice, France.
authors.forename: Joséphine
authors.initials: J
authors.lastname: Parisot
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Sannino
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Russo
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.|Institute of Genetics and Biophysics, CNR, Naples, Italy.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Illingworth
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.|Institute of Biology Valrose, iBV, UMR INSERM1091/CNRS7277/UNS, 06108 Nice, France.|University of Nice Sophia Antipolis (UNS), Nice, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Studer
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.|Institute of Genetics and Biophysics, CNR, Naples, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: De Leonibus
mesh_terms: D000818:Animals; D051838:COUP Transcription Factor I / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051838:COUP Transcription Factor I
keywords: COUP-TFI gradient expression; entorhinal connectivity; hippocampus; septo-temporal longitudinal axis; spatial memory