Retinal horizontal cells: challenging paradigms of neural development and cancer biology - PubMed (original) (raw)
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Retinal horizontal cells: challenging paradigms of neural development and cancer biology
Ross A Poché et al. Development. 2009 Jul.
Abstract
A group of retinal interneurons known as horizontal cells has recently been shown to exhibit a variety of unique biological properties, as compared with other nerve cells, that challenge many long-standing assumptions in the fields of neural development and cancer biology. These features include their unusual migratory behavior, their unique morphological plasticity, and their propensity to divide at a relatively late stage during development. Here, we review these novel features, discuss their relevance for other cell types, outline open questions in our understanding of horizontal cell development and consider their implications.
Figures
Fig. 1.
Horizontal cells in the retina. An adult mouse retina, with horizontal cells (HCs) labeled with an antibody against calbindin (red). This marker labels both the HC somata and their lateral processes within the outer plexiform layer. Neurotrace (blue) identifies all cells within the retina, thereby revealing its laminar cytoarchitecture. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; OS, outer segment.
Fig. 2.
Unusual features of HCs. (A) During embryonic development, retinal progenitor cells (RPCs) undergo mitosis near the outer limiting membrane and subsequently migrate to their appropriate retinal layer. HC precursors do not migrate directly to the prospective HC layer, but rather bypass this layer and migrate basally to the ganglion cell layer (GCL) before changing direction to migrate apically towards the HC layer. This second phase of HC migration has been shown to depend on Lim1. (B) Upon the completion of HC migration, the HCs are organized in a non-random spatial arrangement (mosaic) within the outer retina. HC spacing has been shown to be regulated by homotypic repulsive interactions mediated by transient, apically directed neurites (arrowheads). (C) Zebrafish and chick retinae contain committed progenitor cells that divide to produce only HCs, and in the zebrafish do so within the HC stratum. (D,E) Subsequent to cell cycle exit, homotypic interactions restrain dendritic overlap, as these processes stratify and form synaptic contacts with their afferents in the outer plexiform layer (OPL). (F) In a mouse model of retinoblastoma, fully differentiated HCs re-enter the cell cycle and give rise to aggressively metastatic tumors. ONL, outer nuclear layer; INL, inner nuclear layer; IPL, inner plexiform layer; onbl, outer neuroblastic layer; inbl, inner neuroblastic layer; RPE, retinal pigment epithelium.
Fig. 3.
Transcriptional control of HC and amacrine cell development. The transcription factor Foxn4 lies at the top of the genetic hierarchy that regulates HC and amacrine cell fate determination in mice and probably also in other vertebrates. Downstream of Foxn4, the transcription factor Ptf1a reinforces the decision towards either amacrine or HC fate. The transcription factor Prox1 steers a subset of Ptf1a+ cells towards the HC fate, whereas transcription factors Math3 and NeuroD direct a separate cohort towards the amacrine cell fate. Further downstream in the amacrine cell developmental pathway, the transcription factors Barhl2, Bhlhb5 and Isl1 specify subtypes of amacrine cell. See text for details on the other factors. HC, horizontal cell; AC, amacrine cell; BP, bipolar cell; MG, Müller glial cell; GC, ganglion cell; R, rod photoreceptor; C, cone photoreceptor; RPC, retinal progenitor cell.
Fig. 4.
HCs are non-randomly distributed. (A) The tangential dispersion of immature HCs, as observed in X-inactivation _lacZ_-mosaic mice, was proposed to be the means by which HCs (arrow) and other regularly spaced cell types establish regularity in their patterned distributions. Cells in blue are all derived from the same retinal progenitor cell, revealing the dispersion of particular types of cell from their clonal column of origin. This process is thought to be driven by homotypic interactions between neighboring cells. (B) Viewed from the surface, the HC somata exhibit regular spacing within their stratum in the mature retina. Their dendrites overlap one another (arrow), so that a single cone photoreceptor innervates multiple HCs. (C) A single HC labeled with DiI (within a retinal flat-mount) illustrates HC dendritic morphology. (D) A retinal flat-mount labeled with an antibody against calbindin, which highlights the HC somata and processes and reveals the non-random distribution of these cells across the retina.
Fig. 5.
Differentiated HCs can divide and give rise to retinoblastoma. HCs from Rb-/-; p107+/-; p130-/- mice (referred to as p107-single mice because they carry one normal p107 allele) have been shown to undergo mitosis while in a fully differentiated state whereby HC processes exhibited by the mitotic cell were inherited by the daughter cell.
References
- Bellion, A., Baudoin, J. P., Alvarez, C., Bornens, M. and Metin, C. (2005). Nucleokinesis in tangentially migrating neurons comprises two alternating phases: forward migration of the Golgi/centrosome associated with centrosome splitting and myosin contraction at the rear. J. Neurosci. 25, 5691-5699. -PMC -PubMed
- Belliveau, M. J. and Cepko, C. L. (1999). Extrinsic and intrinsic factors control the genesis of amacrine and cone cells in the rat retina. Development 126, 555-566. -PubMed
- Boije, H., Edqvist, P. H. and Hallbook, F. (2009). Horizontal cell progenitors arrest in G2-phase and undergo terminal mitosis on the vitreal side of the chick retina. Dev. Biol. (in press). -PubMed
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