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Maureen A Peters

Publications and source records attributed to Maureen A Peters.

4 recordsLinked to original sources

Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina.

Asymmetric expression of several genes in the early eye anlagen is required for the dorsoventral (DV) and anteroposterior (AP) patterning of the retina. Some of these early patterning genes play a role in determining the graded expression of molecules that are needed to form the retinotectal map. The polarized expression of retinoic acid synthesizing and degrading enzymes along the DV axis in the retina leads to several zones of varied retinoic acid (RA) activity. This is suggestive of RA playing a role in DV patterning of the retina. A dominant-negative form of the retinoic acid receptor alpha (DNhRARalpha) was expressed in the chick retina to block RA activity. RA signaling was found to play a role in regulating the expression of EphB2, EphB3 and ephrin B2, three molecules whose graded expression in the retina along the DV axis is important for establishing the correct retinotectal map. Blocking RA signaling by misexpression of a RA degrading enzyme, Cyp26A1 recapitulated some but not all the effects of DNhRARalpha. It also was found that Vax, a ventrally expressed transcription factor that regulates the expression of the EphB and ephrin B molecules, functions upstream of, or in parallel to, RA. Expression of DNhRARalpha led to increased levels of RA-synthesizing enzymes and loss of RA-degrading enzymes. Activation of such compensatory mechanisms when RA activity is blocked suggests that RA homeostasis is very strictly regulated in the retina.

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The rod photoreceptor pattern is set at the optic vesicle stage and requires spatially restricted cVax expression.

How and when positional identities in the neural retina are established have been addressed primarily with respect to the topographic projections of retinal ganglion cells onto their targets in the brain. Although retinotectal map formation is a prominent manifestation of retinal patterning, it is not the only one. Photoreceptor subtypes are arranged in distinct, species-specific patterns. The mechanisms used to establish photoreceptor patterns have been relatively unexplored at the mechanistic level. We performed ablations of the eye anlage in chickens and found that removal of the anterior or dorsal optic vesicle caused loss of the area centralis, which is a rod-free central area of the retina, and severely disorganized other aspects of the rod pattern. These observations indicate that the anteroposterior and dorsoventral distribution of rods is determined by the optic vesicle stage. To investigate the molecular mechanisms involved, the rod distribution was analyzed after viral misexpression of several patterning genes that were previously shown to be important in positional specification of retinal ganglion cells. Ectopic expression of FoxG1, SOHo1,or GH6 transcription factors expressed in the anterior optic vesicle and/or optic cup, respectively, did not affect the rod pattern. This pattern therefore appears to be specified by an activity acting before, or in parallel with, these factors. In contrast, misexpression of the ventrally restricted transcription factor, cVax, severely disturbed the rod pattern.

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The dorsal-ventral axis of the neural retina is divided into multiple domains of restricted gene expression which exhibit features of lineage compartments.

The neural retina is a complex sensory structure designed to receive, integrate, and transmit visual information. An important aspect of retinal development is the establishment of pattern along the dorsal-ventral (D-V) and anterior-posterior (A-P) axes. The recent identification and functional characterization of a dorsal-specific and a ventral-specific transcription factor suggested that the D-V axis is divided into two domains. This study characterizes the expression patterns of these and other D-V markers, and establishes that the retina is subdivided into at least four domains of gene expression along this axis. The composition and spatial relation of these expression domains alters our model of D-V patterning, suggesting more complexity in the way that the retina is patterned than was previously recognized. As domains of gene expression within developing tissues sometimes comprise compartments whose borders are not crossed by clonally related cells, we performed a retroviral lineage study. A strong preference for cells to remain in their original domain of gene expression was observed, suggesting that these borders comprise developmental compartments.

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Patterning the neural retina.

The early patterning events that shape the neural retina guide the genesis and distribution of postmitotic cell types, as well as their connectivity. The recent discovery of key signaling pathways and transcription factors involved in establishing central, anterior-posterior, and dorsal-ventral retinal patterning has given us insights into the molecular mechanisms controlling these events.

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