Transient neurites of retinal horizontal cells exhibit columnar tiling via homotypic interactions

Abstract

Sensory neurons with common function are often non-randomly arranged and form dendritic territories that exhibit little overlap or tiling. Repulsive homotypic interactions underlie such patterns in cell organization in invertebrate neurons. In mammalian retinal horizontal cells, however, it is unclear how dendro-dendritic repulsive interactions can produce a non-random distribution of cells and their spatial territories because mature horizontal cell dendrites overlap substantially. By imaging developing mouse horizontal cells, we found that upon reaching their final laminar positions, these cells transiently elaborate vertical neurites that form non-overlapping columnar territories. Targeted cell ablation revealed that the vertical neurites engage in homotypic interactions resulting in tiling of neighboring cells prior to establishment of their dendritic fields. This developmental tiling of transient neurites correlates with the emergence of a non-random distribution of the cells, and could represent a mechanism that organizes neighbor relationships and territories of neurons of the same type before circuit assembly.

Retinal horizontal cells: challenging paradigms of neural development and cancer biology

“…Upon analyzing late embryonic retinae, before HCs have completed their migration to the OPL, one or two apical and basal processes were observed that extended from the somata of GFP + HCs as they migrated radially towards their prospective layer. Also, tangential HC movements, in which somata squeezed through thick, lateral neurites, were seen near the level of the eventual HC layer, confirming the interpretation of previous results from clonal analyses that proposed that discrete cells located outside of their clonal columns must have moved tangentially (see also Cook and Chalupa, 2000).At early postnatal stages, as the HCs settle into their prospective stratum, the vertical neurites were observed to become more numerous and branched, while also exhibiting dynamic extension and retraction every one to two hours (Huckfeldt et al, 2009). Unexpectedly, these radially oriented neurites were confined to distinct columnar territories, and neurites from adjacent cells appeared to be in close physical contact, but displayed minimal overlap (Huckfeldt et al, 2009).…”

“…Unexpectedly, these radially oriented neurites were confined to distinct columnar territories, and neurites from adjacent cells appeared to be in close physical contact, but displayed minimal overlap (Huckfeldt et al, 2009). These non-overlapping neuritic domains also coincided with an increase in intercellular spacing between neighboring HCs, suggesting that transient vertical neurites, rather than lateral dendro-dendritic contacts, participate in the homotypic repulsive interactions that drive mosaic formation (Fig.…”

“…Very recently, an elegant study that employed multi-photon timelapse imaging of embryonic and early postnatal retinae has brought a new level of insight into HC mosaic formation and has resolved some of these issues (Huckfeldt et al, 2009). The authors prepared flat-mounts of acutely isolated retinae from a transgenic mouse line in which HCs are labeled with green fluorescent protein (GFP) driven by the Gad67 (Gad1) promoter (Chattopadhyaya et al, 2004).…”

“…At early postnatal stages, as the HCs settle into their prospective stratum, the vertical neurites were observed to become more numerous and branched, while also exhibiting dynamic extension and retraction every one to two hours (Huckfeldt et al, 2009). Unexpectedly, these radially oriented neurites were confined to distinct columnar territories, and neurites from adjacent cells appeared to be in close physical contact, but displayed minimal overlap (Huckfeldt et al, 2009).…”

“…This degree of retinal 'coverage' is approximated when the dendritic radius approaches the average intercellular spacing. Rather, it suggests that active dendritic extension at the tips could be constrained by contact with the neighboring somata of homotypic cells, but what might mediate this signaling remains to be established.Very recently, an elegant study that employed multi-photon timelapse imaging of embryonic and early postnatal retinae has brought a new level of insight into HC mosaic formation and has resolved some of these issues (Huckfeldt et al, 2009). The authors prepared flat-mounts of acutely isolated retinae from a transgenic mouse line in which HCs are labeled with green fluorescent protein (GFP) driven by the Gad67 (Gad1) promoter (Chattopadhyaya et al, 2004).…”