TALE transcription factors during early development of the vertebrate brain and eye

Schulte, Dorothea; Frank, Dale

doi:10.1002/dvdy.24030

Cited by 33 publications

(29 citation statements)

References 220 publications

(277 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We identified 5761 Pbx and 1410 Meis binding regions (1% IDR) enriched for consensus motifs that correlate with those previously identified in 11.5 day mouse embryos (Penkov et al 2013) ( Supplemental Table S5,6). The larger number of Pbx bound regions compared to Meis is consistent with its more general role as a cofactor for a variety of TFs (Laurent et al 2008;Schulte and Frank 2014). In comparing these genome-wide profiles with Hoxa1 bound regions, a large number also display co-occupancy of Pbx and Meis (Fig.…”

Section: Clustered Binding Sites For Hox Pbx and Meissupporting

confidence: 60%

Hoxa1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on Hoxa1 targets

Kumar

Parker

Paulson

et al. 2016

Preprint

View full text Add to dashboard Cite

Hoxa1 has diverse functional roles in differentiation and development. We have identified and characterized properties of regions bound by Hoxa1 on a genome-wide basis in differentiating mouse ES cells. Hoxa1 bound regions are enriched for clusters of consensus binding motifs for Hox, Pbx and Meis and many display co-occupancy of Pbx and Meis. Pbx and Meis are members of the TALE family and genome-wide analysis of multiple TALE members (Pbx, Meis, TGIF, Prep1 and Prep2) show that nearly all Hoxa1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins defines distinct classes of Hoxa1 targets and indicates a role as cofactors in modulating the specificity of Hox proteins. We also discovered extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes. This study provides new insight into a regulatory network involving combinatorial interactions between Hoxa1 and TALE proteins.

show abstract

Section: Clustered Binding Sites For Hox Pbx and Meissupporting

confidence: 60%

Hoxa1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on Hoxa1 targets

Kumar

Parker

Paulson

et al. 2016

Preprint

View full text Add to dashboard Cite

show abstract

“…The pervasive and dynamic expression of Pbx, Meis, and Prep genes in the mouse embryonic head, in domains patterned by Hox genes, and also in Hox-less territories (for reviews, see Alexander et al 2009;Schulte and Frank 2014) suggested critical roles for these TFs in brain and cranium development. Here we discuss three paradigmatic examples of PBX-depedent processes in head morphogenesis.…”

Section: Control Of Embryonic Development and Onset Of Disease Under mentioning

confidence: 99%

‘Building a perfect body’: control of vertebrate organogenesis by PBX-dependent regulatory networks

2019

View full text Add to dashboard Cite

Pbx genes encode transcription factors that belong to the TALE (three-amino-acid loop extension) superclass of homeodomain proteins. We have witnessed a surge in information about the roles of this gene family as leading actors in the transcriptional control of development. PBX proteins represent a clear example of how transcription factors can regulate developmental processes by combinatorial properties, acting within multimeric complexes to implement activation or repression of transcription depending on their interaction partners. Here, we revisit long-emphasized functions of PBX transcription factors as cofactors for HOX proteins, major architects of the body plan. We further discuss new knowledge on roles of PBX proteins in different developmental contexts as upstream regulators of Hox genes-as factors that interact with non-HOX proteins and can work independently of HOX-as well as potential pioneer factors. Committed to building a perfect body, PBX proteins govern regulatory networks that direct essential morphogenetic processes and organogenesis in vertebrate development. Perturbations of PBX-dependent networks can cause human congenital disease and cancer.

show abstract

“…Thus, besides Ccnd1, Meis1 is likely to regulate additional neurogenic pathways. This regulation must take place via a Hox/Pbx-independent mechanism because Hox genes, which are well-known partners of Meis in the trunk, are not expressed in the head (Schulte and Frank, 2014). Furthermore, there is no indication that Pbx genes contribute to early eye formation, even though compound knockout mice have been generated and extensively studied (Capellini et al, 2011;Stankunas et al, 2008).…”

Section: Microphthalmia Is Not a Consequence Of Meis1 Function In Thementioning

confidence: 99%

“…Members of the Meis subfamily are however also expressed in the brain and sensory organs (Schulte and Frank, 2014), which are Hox-free embryonic regions (Duboule, 2007;Mallo and Alonso, 2013). In particular, Meis1 is expressed in the vertebrate forebrain and sensory organ primordia, including the eye, being essential for the specification of part of these structures.…”

Section: Introductionmentioning

confidence: 99%

Meis1 coordinates a network of genes implicated in eye development and microphthalmia

et al. 2015

View full text Add to dashboard Cite

Microphthalmos is a rare congenital anomaly characterized by reduced eye size and visual deficits of variable degree. Sporadic and hereditary microphthalmos have been associated with heterozygous mutations in genes fundamental for eye development. Yet, many cases are idiopathic or await the identification of molecular causes. Here we show that haploinsufficiency of Meis1, which encodes a transcription factor with evolutionarily conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment in adult mice. By combining analysis of Meis1 loss-offunction and conditional Meis1 functional rescue with ChIP-seq and RNA-seq approaches we show that, in contrast to its preferential association with Hox-Pbx BSs in the trunk, Meis1 binds to Hox/Pbxindependent sites during optic cup development. In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway. In addition, Meis1 is required for eye patterning by controlling a set of eye territory-specific transcription factors, so that in Meis1 −/− embryos boundaries among the different eye territories are shifted or blurred. We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations.

show abstract

TALE transcription factors during early development of the vertebrate brain and eye

Cited by 33 publications

References 220 publications

Hoxa1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on Hoxa1 targets

Hoxa1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on Hoxa1 targets

‘Building a perfect body’: control of vertebrate organogenesis by PBX-dependent regulatory networks

Meis1 coordinates a network of genes implicated in eye development and microphthalmia

Contact Info

Product

Resources

About