Regulation and evolution of cardiopharyngeal cell identity and behavior: insights from simple chordates - PubMed (original) (raw)

Review

Regulation and evolution of cardiopharyngeal cell identity and behavior: insights from simple chordates

Nicole Kaplan et al. Curr Opin Genet Dev. 2015 Jun.

Abstract

The vertebrate heart arises from distinct first and second heart fields. The latter also share a common origin with branchiomeric muscles in the pharyngeal mesoderm and transcription regulators, such as Nkx2-5, Tbx1 and Islet1. Despite significant progress, the complexity of vertebrate embryos has hindered the identification of multipotent cardiopharyngeal progenitors. Here, we summarize recent insights in cardiopharyngeal development gained from ascidian models, among the closest relatives to vertebrates. In a simplified cellular context, progressive fate specification of the ascidian cardiopharyngeal precursors presents striking similarities with their vertebrate counterparts. Multipotent cardiopharyngeal progenitors are primed to activate both the early cardiac and pharyngeal muscles programs, which segregate following asymmetric cells divisions as a result of regulatory cross-antagonisms involving Tbx1 and Nkx2-5 homologs. Activation of Ebf in pharyngeal muscle founder cells triggers both Myogenic Regulatory Factor-associated differentiation and Notch-mediated maintenance of an undifferentiated state in distinct precursors. Cross-species comparisons revealed the deep conservation of the cardiopharyngeal developmental sequence in spite of extreme genome sequence divergence, gene network rewiring and specific morphogenetic differences. Finally, analyses are beginning to uncover the influence of surrounding tissues in determining cardiopharyngeal cell identity and behavior. Thus, ascidian embryos offer a unique opportunity to study gene regulation and cell behaviors at the cellular level throughout cardiopharyngeal morphogenesis and evolution.

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Figures

Figure 1. Schematic representation of cardio-pharyngeal development in Ciona intestinalis

(A) Schematic showing the trunk ventral cell progeny with divisions and migrations (green and blue arrows), from initial tail bud stage (8 hpf) to metamorphosing juvenile (45 hpf). Trunk ventral cells (TVC, green), STVC (secondary TVC, yellow), first heart precursors (FHP, red), atrial siphon muscle founder cells (ASMF, light blue), second heart precursors (SHP, orange), inner and outer ASM precursors (ASMPs, dark blue and violet, respectively), heart (red/orange). The first longitudinal muscle (LoM) derives from the ASM ring. The left side only is presented, linked nuclei indicate sister cells, dashed lines represent the midline. (B) Fluorescent in situ hybridization of key markers of the TVC progeny from 12.5 hpf to 22 hpf. The B7.5 lineage (red) is marked with Mesp>NLS::lacZ revealed by anti β-galactosidase immunostaining. Scale bar, 10 µm. (C) Summary of the ontogenetic interactions of the B7.5 cardiopharyngeal lineage. The TVC are transcriptionally primed pluripotent progenitors (1). Heart (e.g. Gata4/5/6, Hand) and ASM (e.g. Hand-r, Tbx1/10) transcriptional regulatory programs are segregated through cross-antagonisms coupled to asymmetric divisions (2). A myogenic program associated with Mrf is deployed downstream of Ebf, which also promotes Notch-mediated lateral inhibition of Mrf and maintenance of a pool of stem cell-like muscle progenitors (3). Same color code as above.

Figure 2. Variations on a conserved ontogenetic motif: comparison of the cardiopharyngeal development in Ciona intestinalis and Molgula occidentalis

(A) Simplified evolutionary tree of Tunicates based on 18s phylogeny, adapted from [92]. The Ciona and Molgula genera are positioned on the two most divergent branches within Tunicates. (B) Comparative schematic showing the B7.5 lineage in Ciona intestinalis and Molgula occidentalis. In both species, the TVCs (green) migrate away from the ATMs. In Ciona intestinalis, the TVCs converge at the midline of the ventral trunk before they divide into STVCs (yellow) and FHPs (red). In Molgula occidentalis, the TVCs divide more laterally into STVCs and FHPs, resulting in distinct bilateral clusters of heart precursors. In both species, the oral siphon muscle precursors (dark green) derive from a different cell lineage and form a ring surrounding a single oral placode (pink). In Ciona intestinalis, 4 ASMPs migrate towards the atrial placode (pink), divide and from a rings of 8 cells (violet) on either side. In Molgula occidentalis, the absence bilateral atrial placodes causes the ASMPs to remain as two bilateral clusters of cells. (C) Summary of the ontogeny of the B7.5 cardiopharyngeal lineage of Molgula occidentalis. Conservation of the cell division patterns is coupled to conserved spatiotemporal expression patterns of the main markers of the B7.5 lineage. Same color code as above

Figure 3. Model showing asymmetric induction of TVC fate by regional matrix adhesion

(A) Dorsal (top) and lateral (bottom) views of schematic B8.9 and B8.10 founder cells at neurula stage (~7hpf). GFP-tagged actin binding domain of Talin labels actin at adhesive foci (light green), which localize ventrally in founder cells before they divide; black hashes represent matrix adhesion to the underlying epidermis at the ventral border of founder cells. During mitosis, GFP-ABD-Talin foci increase in size and intensity, which correlates with stronger adhesion to the underlying ECM. After cytokinesis (~7.5hpf), two different fates are specified: ATM (gray), and TVC (green). GFP-ABD-Talin foci are inherited by TVCs, and ventral edges of newly born TVCs appear to protrude into the underlying epidermis. (B) Model of regional MAPK activation and asymmetric TVC induction despite uniform FGF exposure. Polarized Rap activity in founder cells leads to regional stabilization of adhesion during cytokinesis at the presumptive TVC membrane in founder cells. Strong differential adhesion in newly born TVCs leads to differential MAPK activity and finally to TVC specification.

Figure 4. Surrounding tissues canalize TVCs towards directional migration

(A) Initial tailbud embryo expressing membrane-localized reporter hCD4::mCherry in the endoderm (red), and GFP in the B7.5 lineage (green). Leader and trailer TVCs are shown. Surface contact analysis between TVC and endoderm indicates that only the presumptive leader TVC contacts the endoderm (blue). Scale bar, 40 µm. (B) Localization of membrane localized protein hCD4::mCherry (red) at cell membranes and KDEL receptor KDELR::GFP (green) labelling the endoplasmic reticulum (ER) in control embryos. Scale bar, 40 µm. (C) In embryos expressing dnSar1, hCD4::mCherry accumulates in the ER and cannot be properly trafficked to the membrane, indicated by the co-localization of red and green at the ER, and the absence of red fluorescence at cell membranes. (D) Schematic mid-tailbud embryo showing TVCs (green) and ATMs (gray) and tissues analyzed by Gline et al. by tissue-specific disruption of the secretory pathway: epidermis (red), mesenchyme (orange), endoderm (yellow) and notochord (blue). Model for extrinsic tissue influences on TVCs and intercellular interactions during TVC migration. The endoderm (yellow) signals to the TVCs (green) to establish leader-trailer polarity and TVCs in turn signal to each other to maintain polarity during migration. The notochord (blue) possibly sends chemorepulsive signals to migrating TVCs. TVCs adhere to each other during migration and also to the underlying epidermis (red) through cell-ECM interactions.

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Regulation and evolution of cardiopharyngeal cell identity and behavior: insights from simple chordates - PubMed (original) (raw)