Evidence for an evolutionary conserved role of<i>homothorax/Meis1/2</i>during vertebrate retina development

Heine, Peer; Dohle, Eva; Bumsted-O'Brien, Keely; Engelkamp, Dieter; Schulte, Dorothea

doi:10.1242/dev.012088

Cited by 85 publications

(146 citation statements)

References 44 publications

(44 reference statements)

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“…This regulatory cascade is strongly supported by a number of observations. Meis2 directly activates Pax6 expression during lens and retina development in the zebrafish, chick, and mouse (16,19,30). In medaka fish embryos, expression levels of olMeis2 and, concomitantly, those of olPax6 and its downstream targets are up-regulated on miR-204 knock-down or inhibition of the miR-204 interaction with its specific target site in the Meis2 3′-UTR.…”

Section: Mir-204 Controls Lens Differentiation By Targeting Meis2 Andmentioning

confidence: 99%

miR-204 is required for lens and retinal development via Meis2 targeting

Conte

Carrella²,

Avellino³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

150

183

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MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in the regulation of gene expression. The roles of individual miRNAs in controlling vertebrate eye development remain, however, largely unexplored. Here, we show that a single miRNA, miR-204, regulates multiple aspects of eye development in the medaka fish (Oryzias latipes). Morpholino-mediated ablation of miR-204 expression resulted in an eye phenotype characterized by microphthalmia, abnormal lens formation, and altered dorsoventral (D-V) patterning of the retina, which is associated with optic fissure coloboma. Using a variety of in vivo and in vitro approaches, we identified the transcription factor Meis2 as one of the main targets of miR-204 function. We show that, together with altered regulation of the Pax6 pathway, the abnormally elevated levels of Meis2 resulting from miR-204 inactivation are largely responsible for the observed phenotype. These data provide an example of how a specific miRNA can regulate multiple events in eye formation; at the same time, they uncover an as yet unreported function of Meis2 in the specification of D-V patterning of the retina.microRNA | eye development | medaka fish

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Section: Mir-204 Controls Lens Differentiation By Targeting Meis2 Andmentioning

confidence: 99%

miR-204 is required for lens and retinal development via Meis2 targeting

Conte

Carrella²,

Avellino³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

150

183

View full text Add to dashboard Cite

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“…cyclinD1 and myca are regulated by meis1 in the chick and zebrafish retina (Bessa et al, 2008;Heine et al, 2008). meis1 is a homeodomain transcription factor that is expressed in retinal progenitor cells in Drosophila and zebrafish and keeps them in a proliferative state and suppresses differentiation (Pai et al, 1998;Bessa et al, 2008;Heine et al, 2008).…”

Section: Developmental Dynamicsmentioning

confidence: 99%

“…meis1 is a homeodomain transcription factor that is expressed in retinal progenitor cells in Drosophila and zebrafish and keeps them in a proliferative state and suppresses differentiation (Pai et al, 1998;Bessa et al, 2008;Heine et al, 2008). In the absence of meis1, cyclinD1 and myca expression rates are reduced, leading to a reduction in proliferation.…”

Section: Developmental Dynamicsmentioning

confidence: 99%

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Loss of adenomatous polyposis coli (apc) results in an expanded ciliary marginal zone in the zebrafish eye

Stephens

Senecal

Nguyen

et al. 2010

Developmental Dynamics

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The distal region of neural retina (ciliary marginal zone [CMZ]) contains stem cells that produce non-neural and neuronal progenitors. We provide a detailed gene expression analysis of the eyes of apc mutant zebrafish where the Wnt/b-catenin pathway is constitutively active. Wnt/b-catenin signaling leads to an expansion of the CMZ accompanied by a central shift of the retinal identity gene sox2 and the proneural gene atoh7. This suggests an important role for peripheral Wnt/b-catenin signaling in regulating the expression and localization of neurogenic genes in the central retina. Retinal identity genes rx1 and vsx2, as well as meis1 and pax6a act upstream of Wnt/b-catenin pathway activation. Peripheral cells that likely contain stem cells can be identified by the expression of follistatin, otx1, and axin2 and the lack of expression of myca and cyclinD1. Our results introduce the zebrafish apc mutation as a new model to study signaling pathways regulating the CMZ.

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“…The distinct cell-fate potentials of ventral midbrain progenitors are defined by domain-identifiable expression of transcription factors. For example, the Lmx1a + Foxa2 + FP exclusively gives rise to mDA neurons, whereas the ventral-lateral domains marked by Meis2, Mab21l2, Helt, and Lhx1 produce glutamatergic or GABAergic neurons (6)(7)(8)(9). Perturbation of such a transcription "code" seen in genetic studies often led to misspecification of progenitor identity and subsequently to neural transmitter phenotypes (10)(11)(12).…”

mentioning

confidence: 99%

Doublesex and mab-3–related transcription factor 5 promotes midbrain dopaminergic identity in pluripotent stem cells by enforcing a ventral-medial progenitor fate

Gennet

Gale

Nan

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Understanding the control of cell-fate choices during embryonic stem cell (ESC) differentiation is crucial for harnessing strategies for efficient production of desired cell types for pharmaceutical drug screening and cell transplantation. Here we report the identification of the zinc finger-like doublesex and mab-3-related transcription factor 5 (Dmrt5) as a marker for mammalian ventralmedial mesencephalic neuroepithelium that give rise to dopamine neurons. Gain-and loss-of-function studies in ESC demonstrate that Dmrt5 is critically involved in the specification of ventralmedial neural progenitor cell fate and the subsequent generation of dopamine neurons expressing essential midbrain characteristics. Genome-wide analysis of Dmrt5-mediated transcriptome changes and expression profiling of ventral-medial and ventral-lateral mesencephalic neuroepithelium revealed suppressive and inductive regulatory roles for Dmrt5 in the transcription program associated with the ventral-medial neural progenitor fates. Together, these data identify Dmrt5 as an important player in ventral mesencephalic neural fate specification.A major goal of embryonic stem cell (ESC) research is to direct the cells' differentiation toward specific cell types, especially those targeted by devastating degenerative diseases. The advent of induced pluripotent stem cell technology, with its promise for disease modeling, drug screening, and cell therapy, places further demand on a better understanding on the control of lineage/cell-fate specification from pluripotent stem cells. One neuronal cell type in particular, the midbrain dopaminergic (mDA) neuron, is a prime target in applied stem cell research because of its association with Parkinson's disease.The mDA neurons are generated in the floor plate (FP) region of the ventral midbrain and are uniquely identified by their coexpression of tyrosine hydroxylase (TH) with the mDA-specific homeobox protein Pitx3 (1, 2). During development, local inductive signals-Shh, FGF8, and Wnt1-induce distinct cell-fate potentials through initiation of transcriptional cascades that govern the subsequent differentiation, migration, and maturation of the ventral-most progenitors into mDA neurons (3-5). The distinct cell-fate potentials of ventral midbrain progenitors are defined by domain-identifiable expression of transcription factors. For example, the Lmx1a + Foxa2 + FP exclusively gives rise to mDA neurons, whereas the ventral-lateral domains marked by Meis2, Mab21l2, Helt, and Lhx1 produce glutamatergic or GABAergic neurons (6-9). Perturbation of such a transcription "code" seen in genetic studies often led to misspecification of progenitor identity and subsequently to neural transmitter phenotypes (10-12). These studies demonstrate the mechanism of cell-fate determination to be a balance of the activation of "specification" programs and the repression of alternative fates, as observed in the spinal cord (13). However, how transcription factors coordinate distinct fate choice in the ventral midbrain remains poorl...

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Evidence for an evolutionary conserved role ofhomothorax/Meis1/2during vertebrate retina development

Cited by 85 publications

References 44 publications

miR-204 is required for lens and retinal development via Meis2 targeting

miR-204 is required for lens and retinal development via Meis2 targeting

Loss of adenomatous polyposis coli (apc) results in an expanded ciliary marginal zone in the zebrafish eye

Doublesex and mab-3–related transcription factor 5 promotes midbrain dopaminergic identity in pluripotent stem cells by enforcing a ventral-medial progenitor fate

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