neurogenesis

• Neurogenesis in the hippocampus occurs in a region called the subgranular zone (SGZ), which is located within the dentate gyrus.
• The primary cell type involved in neurogenesis is the radial glial-like stem cell, known as the radial astrocyte or type-1 cell.
• Upon activation, these cells give rise to intermediate progenitor cells (type-2 cells) that undergo limited divisions.
• Intermediate progenitors give rise to neuroblasts (type-3 cells), which migrate into the granule cell layer.
• Neuroblasts differentiate into mature granule neurons, integrating into the existing hippocampal circuitry.
• The newly generated neurons become granule cells, contributing to the function of the dentate gyrus in processes related to learning and memory.
• Neurogenesis occurs in the SVZ lining the lateral ventricles.
• In this region, the stem cells are called B cells (type-B astrocytes), which are quiescent and serve as the primary neural stem cells.
• Upon activation, type-B astrocytes become activated and give rise to transit-amplifying cells (type-C cells).
• Type-C cells generate neuroblasts (type-A cells), which migrate along the rostral migratory stream (RMS) toward the olfactory bulb.
• Neuroblasts differentiate into interneurons in the olfactory bulb, integrating into the local circuitry.
• The newly generated neurons become interneurons, primarily granule cells and periglomerular cells, contributing to olfactory information processing.
• While the mammalian retina does not exhibit widespread neurogenesis in adulthood, there is evidence of continuous generation of certain cell types, particularly in the inner nuclear layer.
• Müller glial cells in the retina have been shown to display some characteristics of stem cells and can give rise to new neurons, including bipolar cells, under certain experimental conditions or in response to injury.
• This process is limited compared to the robust neurogenesis observed in the hippocampus and SVZ.
• The majority of retinal neurons are generated during embryonic and early postnatal development.
• One experimental strategy for generating retinal neurons in vitro involves the use of induced pluripotent stem cells (iPSCs) derived from somatic cells.
• This approach allows researchers to reprogram adult cells into a pluripotent state, from which they can then differentiate into various cell types, including retinal neurons.
• Induction of Pluripotency: Select somatic cells (such as skin fibroblasts) from a donor organism.
• Introduce pluripotency-inducing factors, such as Oct4, Sox2, Klf4, and c-Myc, through viral vectors or other delivery methods.
• Cultivate the reprogrammed cells, now iPSCs, in conditions that promote pluripotency.
• Directed Differentiation into Retinal Progenitors: Expose iPSCs to a series of differentiation cues that mimic the developmental processes guiding retinal development in vivo.
• Sequentially activate signaling pathways and use specific growth factors to drive the iPSCs toward a retinal lineage.
• Establish a neural progenitor cell population with a focus on the retinal lineage.
• Formation of Retinal Organoids: Encourage the formation of three-dimensional structures called retinal organoids.
• Embed the retinal progenitor cells in a supportive culture environment that allows them to self-organize into structures resembling the developing retina.
• Mimic the cellular and spatial organization seen in the developing retina by providing appropriate culture conditions.
• Maturation of Retinal Neurons: Facilitate the maturation of retinal neurons within the organoids.
• Continue the differentiation process, guiding the retinal progenitors to generate various retinal cell types, including photoreceptors, retinal ganglion cells, bipolar cells, and others.
• Provide appropriate cues and factors to promote synaptogenesis and functional connectivity between the generated neurons.
• Functional Characterization: Assess the functionality of the generated retinal neurons by performing electrophysiological recordings, calcium imaging, and other functional assays.
• Confirm the expression of specific markers for different retinal cell types using immunostaining and molecular analysis techniques.
• Applications and Disease Modeling: Utilize the in vitro generated retinal neurons for disease modeling, drug screening, or potential transplantation therapies.
• Investigate the molecular and cellular mechanisms underlying retinal development and diseases by comparing the characteristics of in vitro-generated retinal neurons with those from normal and diseased tissues.