Pbx1 is required for adult SVZ neurogenesis

Grebbin, Britta Moyo; Hau, Ann-Christin; Groß, Anja; Anders-Maurer, Marie; Schramm, Jasmine; Koss, M. B.; Wille, Christoph; Mittelbronn, Michel; Selleri, Licia; Schulte, Dorothea

doi:10.1242/dev.128033

Cited by 42 publications

(63 citation statements)

References 62 publications

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“…Of note, the findings discussed above in zebrafish demonstrate that the hoxb1a promoter is marked with the active histone modification H3K27ac and thus is primed for transcription prior to Pbx binding. Recent studies have also established that PBX1 controls early neurogenesis partly via the direct regulation of the target gene doublecortin (Dcx) (Grebbin et al 2016). In undifferentiated neural progenitor cells in culture, PBX1 binds the promoter/proximal enhancer of Dcx while the latter is still compacted to histone H1 and apparently before it is significantly marked by activating histone modifications, long before Dcx is expressed.…”

Section: Partnerships Of Pbc Tfsmentioning

confidence: 99%

“…As demonstrated by loss of function (LOF) in mice, different Pbx genes play fundamental and pleiotropic roles in organogenesis. Pbx1 homozygous mutant embryos (Pbx1 −/− ) die in utero with dramatic abnormalities in multiple organs DiMartino et al 2001;Kim et al 2002;Manley et al 2004;Brendolan et al 2005;Capellini et al 2006Capellini et al , 2008Capellini et al , 2010Capellini et al , 2011aStankunas et al 2008;Ferretti et al 2011;Vitobello et al 2011;Koss et al 2012;Hurtado et al 2015;Grebbin et al 2016;Villaescusa et al 2016;Losa et al 2018;McCulley et al 2018;Welsh et al 2018). In contrast, Pbx2 −/− mice do not display detectable abnormalities , while Pbx3 −/− mutants die perinatally, from central respiratory failure ).…”

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

confidence: 99%

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

2019

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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.

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Section: Partnerships Of Pbc Tfsmentioning

confidence: 99%

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

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“…; Grebbin et al. ). We therefore propose the latter scenario as a possible mechanism by which PBX factors coordinate the sequential morphogenesis of the primary and secondary palate.…”

Section: Discussionmentioning

confidence: 97%

Pbx loss in cranial neural crest, unlike in epithelium, results in cleft palate only and a broader midface

et al. 2018

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Orofacial clefting represents the most common craniofacial birth defect. Cleft lip with or without cleft palate (CL/P) is genetically distinct from cleft palate only (CPO). Numerous transcription factors (TFs) regulate normal development of the midface, comprising the premaxilla, maxilla and palatine bones, through control of basic cellular behaviors. Within the Pbx family of genes encoding Three Amino‐acid Loop Extension (TALE) homeodomain‐containing TFs, we previously established that in the mouse, Pbx1 plays a preeminent role in midfacial morphogenesis, and Pbx2 and Pbx3 execute collaborative functions in domains of coexpression. We also reported that Pbx1 loss from cephalic epithelial domains, on a Pbx2‐ or Pbx3‐deficient background, results in CL/P via disruption of a regulatory network that controls apoptosis at the seam of frontonasal and maxillary process fusion. Conversely, Pbx1 loss in cranial neural crest cell (CNCC)‐derived mesenchyme on a Pbx2‐deficient background results in CPO, a phenotype not yet characterized. In this study, we provide in‐depth analysis of PBX1 and PBX2 protein localization from early stages of midfacial morphogenesis throughout development of the secondary palate. We further establish CNCC‐specific roles of PBX TFs and describe the developmental abnormalities resulting from their loss in the murine embryonic secondary palate. Additionally, we compare and contrast the phenotypes arising from PBX1 loss in CNCC with those caused by its loss in the epithelium and show that CNCC‐specific Pbx1 deletion affects only later secondary palate morphogenesis. Moreover, CNCC mutants exhibit perturbed rostro‐caudal organization and broadening of the midfacial complex. Proliferation defects are pronounced in CNCC mutants at gestational day (E)12.5, suggesting altered proliferation of mutant palatal progenitor cells, consistent with roles of PBX factors in maintaining progenitor cell state. Although the craniofacial skeletal abnormalities in CNCC mutants do not result from overt patterning defects, osteogenesis is delayed, underscoring a critical role of PBX factors in CNCC morphogenesis and differentiation. Overall, the characterization of tissue‐specific Pbx loss‐of‐function mouse models with orofacial clefting establishes these strains as unique tools to further dissect the complexities of this congenital craniofacial malformation. This study closely links PBX TALE homeodomain proteins to the variation in maxillary shape and size that occurs in pathological settings and during evolution of midfacial morphology.

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“…Because of the redundancy of, and early requirements for, Pbx proteins in mouse embryogenesis (reviewed in Selleri et al 2019), we needed to make use of conditional loss-offunction in Myf5 Cre/+ ;Pbx1 fl/fl ;Pbx2 -/compound mutants. A similar approach, using different conditional Cre lines, has previously been taken to study Pbx functions in craniofacial, spleen, and spinal cord motor neuron development and in adult neurogenesis (Ferretti et al, 2011;Grebbin et al, 2016;Hanley et al, 2016;Koss et al, 2012;Losa et al, 2018;Welsh et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

Farr¹,

Risolino

et al. 2020

Preprint

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Vertebrate skeletal muscles are composed of both slow-twitch and fast-twitch fiber types. How the differentiation of distinct fiber types is activated during embryogenesis is not well characterized. Skeletal muscle differentiation is initiated by the activity of the myogenic basic helix-loop-helix (bHLH) transcription factors Myf5, Myod1, Myf6, and Myog. Myod1 functions as a muscle master regulatory factor and directly activates muscle differentiation genes, including those specific to both slow and fast muscle fibers. Our previous studies showed that Pbx TALE-class homeodomain proteins bind with Myod1 on the promoter of the zebrafish fast muscle gene mylpfa and are required for proper activation of mylpfa expression and the fasttwitch muscle-specific differentiation program in zebrafish embryos. Pbx proteins have also been shown to bind regulatory regions of muscle differentiation genes in mammalian muscle cells in culture. Here, we use new zebrafish mutant strains to confirm the essential roles of zebrafish Pbx factors in embryonic fast muscle differentiation. Furthermore, we examine the requirements for Pbx genes in mouse embryonic skeletal muscle differentiation, an area that has not been investigated in the mammalian embryo. Removing Pbx1 function from skeletal muscle in Myf5 Cre/+; Pbx1 fl/fl mouse embryos has minor effects on embryonic muscle development.However, concomitantly deleting Pbx2 function in Myf5 Cre/+ ;Pbx1 fl/fl ;Pbx2 -/mouse embryos causes delayed activation and reduced expression of fast muscle differentiation genes. In the mouse, Pbx1/Pbx2-dependent fast muscle genes closely match those that have been previously shown to be dependent on murine Six1 and Six4. This work establishes evolutionarily conserved requirements for Pbx factors in embryonic fast muscle differentiation. Our studies are revealing how Pbx homeodomain proteins help direct specific cellular differentiation pathways.

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Pbx1 is required for adult SVZ neurogenesis

Cited by 42 publications

References 62 publications

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

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

Pbx loss in cranial neural crest, unlike in epithelium, results in cleft palate only and a broader midface

Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

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