Culhalik Dilek, Gellisch Morris, Morosan-Puopolo Gabriela, Saberi Darius
Department of Anatomy and Molecular Embryology, Institute of Anatomy, Ruhr-University, Bochum, Germany.
Faculty of Health, Department of Operative Dentistry and Preventive Dentistry, Witten/Herdecke University, Witten, Germany.
Cells Tissues Organs. 2025;214(2):96-103. doi: 10.1159/000540440. Epub 2024 Aug 27.
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.
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.
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.
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.
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.
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.
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.
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.
碱性螺旋-环-螺旋（bHLH）转录因子在多种器官中表达，并参与多种发育过程。小鼠无调蛋白同源物8（Atoh8）是一种bHLH转录因子，在多种发育过程中发挥关键作用，尤其是作为视网膜神经发生的调节因子。此外，已在中枢神经系统中观察到Atoh8的表达。Atoh8在出生后神经发生过程中的功能仍不清楚。
本研究聚焦于阐明Atoh8对大脑出生后神经发生的影响，特别是在不同生命阶段的选定区域：脑室下区（SVZ）、嘴侧迁移流（RMS）和嗅球（OB），使用雄性纯合Atoh8基因敲除（M6KO）小鼠。我们的形态计量分析基于免疫组织化学标记的成神经细胞标志物（双皮质素）、增殖标志物（磷酸化组蛋白H3，PHH3）以及泛神经元标志物。
在Atoh8基因敲除小鼠中，可以观察到出生后神经发生的改变。免疫组织化学分析显示，与野生型小鼠相比，新生M6KO小鼠SVZ内双皮质素阳性成神经细胞显著减少。有趣的是，在成神经细胞随后通过RMS迁移至OB的过程中，未观察到细胞数量和分布的差异。在新生和幼年M6KO小鼠的SVZ和RMS中，增殖的PHH3阳性神经祖细胞的增殖率均显著降低。此外，在OB的肾小球层，新生期检测到的神经元明显较少。
总之，Atoh8是大脑出生后神经发生的正向调节因子。其作用包括促进成神经细胞形成、调节增殖率、分化以及维持成熟神经元。了解Atoh8功能的复杂性为神经发生的复杂调节机制提供了有价值的见解。
碱性螺旋-环-螺旋（bHLH）转录因子在多种器官中表达，并参与多种发育过程。小鼠无调蛋白同源物8（Atoh8）是一种bHLH转录因子，在多种发育过程中发挥关键作用，尤其是作为视网膜神经发生的调节因子。此外，已在中枢神经系统中观察到Atoh8的表达。Atoh8在出生后神经发生过程中的功能仍不清楚。
本研究聚焦于阐明Atoh8对大脑出生后神经发生的影响，特别是在不同生命阶段的选定区域：脑室下区（SVZ）、嘴侧迁移流（RMS）和嗅球（OB），使用雄性纯合Atoh8基因敲除（M6KO）小鼠。我们的形态计量分析基于免疫组织化学标记的成神经细胞标志物（双皮质素）、增殖标志物（磷酸化组蛋白H3，PHH3）以及泛神经元标志物。
在Atoh8基因敲除小鼠中，可以观察到出生后神经发生的改变。免疫组织化学分析显示，与野生型小鼠相比，新生M6KO小鼠SVZ内双皮质素阳性成神经细胞显著减少。有趣的是，在成神经细胞随后通过RMS迁移至OB的过程中，未观察到细胞数量和分布的差异。在新生和幼年M6KO小鼠的SVZ和RMS中，增殖的PHH3阳性神经祖细胞的增殖率均显著降低。此外，在OB的肾小球层，新生期检测到的神经元明显较少。
总之，Atoh8是大脑出生后神经发生的正向调节因子。其作用包括促进成神经细胞形成、调节增殖率、分化以及维持成熟神经元。了解Atoh8功能的复杂性为神经发生的复杂调节机制提供了有价值的见解。
