The Effects of Atoh8 on Postnatal Murine Neurogenesis

Abstract

Introduction: Basic helix-loop-helix (bHLH) transcription factors are expressed in various organs and are involved in diverse developmental processes. The mouse atonal homolog 8 (Atoh8), a bHLH transcription factor, plays a crucial role in various developmental processes, especially as a regulator of neurogenesis in the retina. Besides, Atoh8 expression has been observed in the central nervous system. The function of Atoh8 during the postnatal neurogenesis is still unclear. Methods: This study focuses on elucidating the impact of Atoh8 on postnatal neurogenesis in the brain, particularly in selected regions: the subventricular zone (SVZ), rostral migratory stream (RMS), and olfactory bulb (OB), across different life stages, using male homozygous Atoh8-knockout (M6KO) mice. Our morphometric analysis is based on immunohistochemically labeled markers for neuroblasts (doublecortin) and proliferation (phospho-histone H3, PHH3) as well as pan neuronal markers. Results: In Atoh8−/− mice, alteration in the postnatal neurogenesis can be observed. Immunohistochemical analysis revealed a significant reduction in doublecortin-positive neuroblasts within the SVZ of neonatal M6KO mice compared to wild-type mice. Interestingly, no differences in cell number and distribution were observed in the subsequent migration of neuroblasts through the RMS to the OB. Proliferating PHH3-positive neuronal progenitor cells were significantly diminished in the proliferation rate in both the SVZ and RMS of neonatal and young M6KO mice. Furthermore, in the glomerular layer of the OB, significantly fewer neurons were detected in the neonatal stage. Conclusion: In conclusion, Atoh8 emerges as a positive regulator of postnatal neurogenesis in the brain. Its role encompasses the promotion of neuroblast formation, modulation of proliferation rates, differentiation, and maintenance of mature neurons. Understanding the intricacies of Atoh8 function provides valuable insights into the complex regulatory mechanisms governing neurogenesis.