Intrinsic control of mammalian retinogenesis
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Cellular and Molecular Life Sciences
REVIEW
Intrinsic control of mammalian retinogenesis Mengqing Xiang
Received: 20 August 2012 / Revised: 25 September 2012 / Accepted: 27 September 2012 Ó Springer Basel 2012
Abstract The generation of appropriate and diverse neuronal and glial types and subtypes during development constitutes the critical first step toward assembling functional neural circuits. During mammalian retinogenesis, all seven neuronal and glial cell types present in the adult retina are specified from multipotent progenitors by the combined action of various intrinsic and extrinsic factors. Tremendous progress has been made over the past two decades in uncovering the complex molecular mechanisms that control retinal cell diversification. Molecular genetic studies coupled with bioinformatic approaches have identified numerous transcription factors and cofactors as major intrinsic regulators leading to the establishment of progenitor multipotency and eventual differentiation of various retinal cell types and subtypes. More recently, noncoding RNAs have emerged as another class of intrinsic factors involved in generating retinal cell diversity. These intrinsic regulatory factors are found to act in different developmental processes to establish progenitor multipotency, define progenitor competence, determine cell fates, and/or specify cell types and subtypes. Keywords Retinogenesis Retinal progenitor cell Transcription factor Non-coding RNA Dll4-Notch signaling Foxn4
M. Xiang (&) Center for Advanced Biotechnology and Medicine, Rutgers University, 679 Hoes Lane West, Piscataway, NJ 08854, USA e-mail: [email protected] M. Xiang Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane West, Piscataway, NJ 08854, USA
Introduction The mammalian retina is a delicate multilayered sensorineural epithelium composed of six major types of neurons and one type of glia, the Mu¨ller cells (Fig. 1c). The neuronal types include the rod and cone cells as photoreceptors, the horizontal, bipolar and amacrine cells as interneurons, and the retinal ganglion cells (RGCs) as output neurons. Except for rods, all major types of retinal neurons consist of two or more subtypes that differ in morphologies, physiological properties, and/or sublaminar positions, with amacrine cells and RGCs as the most diversified cell types [1–4]. During embryogenesis, retina originates from the optic vesicle, a protrusion of the neuroepithelium of the neural tube at the diencephalon level. Following invagination of the optic vesicle, a double-layered optic cup is formed with the inner layer containing multipotent retinal progenitor cells (RPCs) capable of differentiating into any of the seven neuronal and glial cell types (Fig. 1a, b). Producing proper types and quantity of retinal cells constitutes the critical first step toward assembling a functional retinal circuitry. A central question in retinal development is, thus, how these diverse cell types and subtypes are specified and differentiated from the
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