Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development

Harrelson, Zachary; Kelly, Robert G.; Goldin, Sarah N.; Gibson‐Brown, Jeremy J.; Bollag, Roni J.; Silver, Lee M.; Papaioannou, Virginia E.

doi:10.1242/dev.01378

Cited by 274 publications

(283 citation statements)

References 61 publications

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“…The lor p25bbtl phenotype demonstrates many features opposite to those observed in enhanced S-cone syndrome and mutations of Nr2e3 or Nrl in mice. Genetic analysis revealed that lor p25bbtl is an allele of tbx2b, a T-box TF with essential roles in development (19)(20)(21)(22). Our data suggest that during photoreceptor cell differentiation, tbx2b acts cell-autonomously to promote the UV-cone fate by repressing the rod fate in zebrafish photoreceptor cell progenitors.…”

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confidence: 72%

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Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development

Álvarez-Delfín

Morris

Snelson

et al. 2009

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

136

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The vertebrate rod and cone photoreceptors are highly specialized sensory neurons that transduce light into the chemical and electrical signals of the nervous system. Although the physiological properties of cones and rods are well known, only a handful of genes have been identified that regulate the specification of photoreceptor subtypes. Taking advantage of the mosaic organization of photoreceptors in zebrafish, we report the isolation of a mutation resulting in a unique change in photoreceptor cell fate. Mutation of the lots-of-rods (lor) locus results in a near one-for-one transformation of UV-cone precursors into rods. The transformed cells exhibit morphological characteristics and a gene-expression pattern typical of rods, but differentiate in a temporal and spatial pattern consistent with UV-cone development. In mutant larvae and adults, the highly ordered photoreceptor mosaic is maintained and degeneration is not observed, suggesting that lor functions after the specification of the other photoreceptor subtypes. In genetic chimeras, lor functions cell-autonomously in the specification of photoreceptor cell fate. Linkage analysis and geneticcomplementation testing indicate that lor is an allele of tbx2b/fby (from beyond). fby was identified by a pineal complex phenotype, and carries a nonsense mutation in the T-box domain of the tbx2b transcription factor. Homozygous fby mutant larvae and lor/fby transheterozygotes also display the lots-of-rods phenotype. Based upon these data, we propose a previously undescribed function for tbx2b in photoreceptor cell precursors, to promote the UV cone fate by repressing the rod differentiation pathway.cone ͉ Danio rerio ͉ T-box ͉ mosaic V ertebrates have evolved 2 major classes of retinal photoreceptors: rods, which mediate dim light vision, and cones, which detect light of greater intensity, have a faster temporal resolution, and mediate color vision. Largely from the analysis of mutations in mice and humans, a transcriptional network regulating photoreceptor cell development has been proposed. The presumptive photoreceptor progenitors sequentially express the homeobox transcription factors (TFs) Otx2 and Crx (1-3), and in their absence, photoreceptor precursors are not specified or fail to differentiate. Rod specification requires the additional expression of the Maf-family TF Nrl and its target Nr2e3 (4, 5). Nrl acts as a molecular switch; in its absence, precursors adopt the short-wavelength (S) opsin cone fate (5, 6), and mis-and over-expression of Nrl transforms most if not all cone precursors into functional rods (7,8). NR2E3 expression, which is disrupted in enhanced S-cone syndrome in humans and the rd7 mouse, is required for the repression of cone-specific genes in rod precursors (4, 9, 10). However, it remains to be determined if a reciprocal system exists in cone precursors for repressing rodspecific genes.The zebrafish retina, in addition to rods, possesses 4 cone subtypes, each with a distinct morphology and expressing a unique opsin (11-17). The spatial...

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confidence: 72%

“…1G), where tbx4 and tbx2b/fby were localized (21). tbx2b is a TF mainly associated with transcriptional repression during cell cycle control, limb, heart and endoderm development (19,20,22), and cancer (25). A single mutant allele of tbx2b has been reported in zebrafish.…”

Section: Resultsmentioning

confidence: 99%

Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development

Álvarez-Delfín

Morris

Snelson

et al. 2009

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

136

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“…6). In the mouse, Tbx2 distribution is also restricted to the dorsal retina and a knockout line has recently been reported in which cardiac defects were characterized (36). It will be interesting to examine the retinas of these embryos to determine whether Tbx2 plays a similar role in asymmetrically regulating retinal neuron differentiation in mammals.…”

Section: Discussionmentioning

confidence: 99%

Tbx2b is essential for neuronal differentiation along the dorsal/ventral axis of the zebrafish retina

Gross

Dowling

2005

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

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The mechanisms by which retinal neurons are patterned along the dorsal͞ventral axis remain largely unknown, yet this patterning is integral for the topographic mapping of visual space. With an interest in elucidating the mechanisms that regulate the development of this retinal axis, we have characterized a T-box family transcription factor, Tbx2b, during zebrafish retinogenesis. Tbx2b is expressed throughout all phases of retinal development with a striking asymmetry of distribution highest dorsally to lowest ventrally. To examine Tbx2b function during retinal development, two morpholino antisense oligonucleotides were created; one blocking the translational start site of Tbx2b and the other interfering with Tbx2b mRNA splicing. Injection of either of these morpholinos resulted in profound defects in the development of the dorsal retina. By using molecular markers for neuronal subtypes, the ventral retina contained all cell types, whereas in the dorsal retina, only retinal ganglion cells expressed markers of differentiation. The cells of the dorsal retina were postmitotic, however, as demonstrated by a lack of BrdUrd incorporation during the normal periods of retinal differentiation. Markers for dorsal and ventral retinal compartments were also expressed normally in Tbx2b morphants. Combined, these observations suggest that the cellular mechanisms regulating neuronal differentiation within the retina are asymmetric about the dorsal͞ventral axis and that Tbx2b mediates this process within the dorsal retina.T-box ͉ retinal development

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“…Strikingly, misexpression of Hand2, Gli3, and Shh are among the first events observed, further suggesting that Tbx3 lies upstream in the gene expression cascade involved in limb AP polarization. Tbx2 mutation, on the other side, leads to a digit 4 bifurcation (Harrelson et al, 2004). This finding may be more related to the role Tbx2 and Tbx3 play a role in local morphogenesis of digits downstream of the interdigital BMP signaling (Suzuki et al, 2004) The HoxD cluster plays a major role in digit formation, in conjunction with paralogous genes of the HoxA cluster.…”

Section: Role Of Tbx Genes In Specification Of More Posterior Identitymentioning

confidence: 99%

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

Robert

Lallemand

2006

Developmental Dynamics

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The limb has been a privileged object of investigation and reflection for scientists over the past two centuries and continues to provide a heuristic framework to analyze vertebrate development. Recently, accumulation of new data has significantly changed our view on the mechanisms of limb patterning, in particular along the anterior-posterior axis. These data have led us to revisit the mode of action of the zone of polarizing activity. They shed light on the molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling pathway and give insights into the mechanism of activation of these cardinal factors, as well as the consequences of their activity. These new data are in good part the result of systematic Application of tools used in contemporary mouse molecular genetics. These have extended the power of mouse genetics by introducing mutational strategies that allow fine-tuned modulation of gene expression, interchromosomal deletions and duplication. They have even made the mouse embryo amenable to cell lineage analysis that used to be the realm of chick embryos. In this review, we focus on the data acquired over the last five years from the analysis of mouse limb development and discuss new perspectives opened by these results. Developmental Dynamics 235:2337-2352, 2006.

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Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development

Cited by 274 publications

References 61 publications

Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development

Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development

Tbx2b is essential for neuronal differentiation along the dorsal/ventral axis of the zebrafish retina

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

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