THE TRANSCRIPTION FACTOR SOX4 CONTROLS THE MORPHOLOGICAL DEVELOPMENT OF ADULT-BORN HIPPOCAMPAL NEURONS

Sox4, together with Sox11 and 12, are transcription factors belonging to the SoxC class. Members of this group have emerged as key components to a wide array of function in neurodevelopmental processes, including migration, dendritogenesis, and neuronal specification. At first, mostly due to their high degree of sequence homology, SoxC genes were originally assumed to act redundantly, with largely overlapping functions. However, recent emerging evidence revealed that individual SOX4 or SOX11 haploinsufficiency produces distinct neurodevelopmental defects in human and their potential unique function in adult neurogenesis is yet to be explored.
SoxC proteins have also been shown to play a role in adult neurogenesis. Sox4/11 start to become highly expressed in activated radial stem cells and their expression persists in immature neurons, until they integrate into pre-existing circuits. Our preliminary data had already revealed that Sox4/11 conditional double knock-out (cDKO) stifle neurogenesis and in this context our goal is to unveil the individual contribution of Sox4. To develop a deeper understanding on this potential distinct function in adult neurogenesis, we adopted a murine tamoxifen-inducible KO model that ablates Sox4 from radial glia-like neural stem cells (NSC). We found that cKO of Sox4 alone, although without significantly altering the number immature neurons formation, produces morphologically abnormal cells, with immature neurites polarity.
Ongoing experiments are now investigating whether the defects in neuronal morphology and polarity observed in vivo can be recapitulated in vitro and we are performing transcriptomic analyses to identify Sox4 potential targets and downstream molecular cascades underlying such morphological alterations.