Upstream regulation for initiation of restricted <i>Shh</i> expression in the chick limb bud

Matsubara, Haruka; Saito, Daisuke; Abe, Gembu; Yokoyama, Hitoshi; Suzuki, Takayuki; Tamura, Koji

doi:10.1002/dvdy.24493

Cited by 10 publications

(8 citation statements)

References 111 publications

(153 reference statements)

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“…Using an antisense-probe (~1000 bp) that was a gift from the Tanaka lab (IMP, Austria), we determined that Shh was first expressed at stage 45 in a posteriorly restricted domain and persisted through stage 49 in a posterior-proximal position (Figure 2A). Compared to anuran and other amniote forelimb buds where Shh expression precedes expression of Hoxd11 , the onset of Shh expression in axolotls appeared relatively late and after Hoxd11 expression (Matsubara et al, 2017; Riddle et al, 1993) (Figure 2—figure supplement 2). While the posterior Shh expression pattern was consistent with previous reports using relatively short probes at several stages (Bickelmann et al, 2018; Imokawa and Yoshizato, 1997; Torok et al, 1999), we also observed Shh expression in an anteriorly restricted domain at stages 46, 47 and 48 (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

“…Second, salamander forelimb buds exhibit a proximal-anterior domain of Shh expression that emerges as the axolotl limb bud begins to bend posteriorly; a domain which is not found during normal limb development in amniotes and anurans. Third, posterior Shh expression corresponding to the ZPA remains in a relatively small proximal domain (Torok et al, 1999) rather than the elongated expression domain found in other tetrapods that extends the proximal-distal length of the autopod (Matsubara et al, 2017; Riddle et al, 1993; Shapiro et al, 2003). With respect to the first point, previous work has demonstrated that flank tissue surrounding the limb field plays an important role in specifying the anteroposterior axis and thus, the temporal appearance of Shh expression may be less important than its posterior induction (Stocum and Fallon, 1982).…”

Section: Discussionmentioning

confidence: 95%

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Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development

Purushothaman

Elewa

Seifert

2019

eLife

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Although decades of studies have produced a generalized model for tetrapod limb development, urodeles deviate from anurans and amniotes in at least two key respects: their limbs exhibit preaxial skeletal differentiation and do not develop an apical ectodermal ridge (AER). Here, we investigated how Sonic hedgehog (Shh) and Fibroblast growth factor (Fgf) signaling regulate limb development in the axolotl. We found that Shh-expressing cells contributed to the most posterior digit, and that inhibiting Shh-signaling inhibited Fgf8 expression, anteroposterior patterning, and distal cell proliferation. In addition to lack of a morphological AER, we found that salamander limbs also lack a molecular AER. We found that amniote and anuran AER-specific Fgfs and their cognate receptors were expressed entirely in the mesenchyme. Broad inhibition of Fgf-signaling demonstrated that this pathway regulates cell proliferation across all three limb axes, in contrast to anurans and amniotes where Fgf-signaling regulates cell survival and proximodistal patterning.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development

Purushothaman

Elewa

Seifert

2019

eLife

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“…Several targets known to be upstream of SHH expression, including Homeobox D9 [ 34 , 35 ], ELF2 (a member of the ETS family), and HAND2 (a basic helix–loop–helix transcription factor) were up-regulated 2.3-fold, 1.9-fold, and 1.6-fold, respectively. A complex interaction between HOX, PBX, ETS, and HAND2 has been implicated in the activation and localization of SHH expression to the ZPA [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development

Watson

Feenstra

Arsdale

et al. 2018

JDB

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During limb development, fibroblast growth factors (Fgfs) govern proximal–distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal–distal and anterior–posterior axes by maintaining Sonic hedgehog (Shh) expression in cells of the zone of polarizing activity (ZPA) in the distal posterior mesoderm. Shh, in turn, maintains Fgfs in the apical ectodermal ridge (AER) that caps the distal tip of the limb bud. Crosstalk between Fgf and Shh signaling is critical for patterned limb development, but the mechanisms underlying this feedback loop are not well-characterized. Implantation of Fgf beads in the proximal posterior limb bud can maintain SHH expression in the former ZPA domain (evident 3 h after application), while prolonged exposure (24 h) can induce SHH outside of this domain. Although temporally and spatially disparate, comparative analysis of transcriptome data from these different populations accentuated genes involved in SHH regulation. Comparative analysis identified 25 candidates common to both treatments, with eight linked to SHH expression or function. Furthermore, we demonstrated that LHX2, a LIM Homeodomain transcription factor, is an intermediate in the FGF-mediated regulation of SHH. Our data suggest that LHX2 acts as a competency factor maintaining distal posterior SHH expression subjacent to the AER.

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“…In contrast, the feather follicle in the FFF region deeply sinks to the posterior-dorsal surface of the bone. Although the mechanism of epithelial invagination of a feather bud in the FFF region is largely unknown, an interesting report by Lin et al [13] suggested that tubular invagination is achieved through loosening of the bud mesenchyme. Epithelial cell proliferation and elongation in the bud may lead to the formation of a sprout that invades the surrounding loosened mesenchyme, and epithelial-mesenchymal interaction may contribute to the epithelium organization as seen in the morphogenesis of other types of epithelial tissues such as mammary glands [25].…”

Section: Discussionmentioning

confidence: 99%

“…Forelimb buds and a square of abdominal skin with hypodermal tissues were excised from staged chicken embryos and processed for whole-mount in situ hybridization as described previously [12] using antisense RNA probes for chick shh (see [12, 13] for detailed information of shh RNA probes). In the later stages of feather morphogenesis, shh is expressed in the marginal plate epithelium that will undergo cell death, providing spaces between the barbs [14–16].…”

Section: Methodsmentioning

confidence: 99%

Flight feather development: its early specialization during embryogenesis

et al. 2018

Self Cite

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BackgroundFlight feathers, a type of feather that is unique to extant/extinct birds and some non-avian dinosaurs, are the most evolutionally advanced type of feather. In general, feather types are formed in the second or later generation of feathers at the first and following molting, and the first molting begins at around two weeks post hatching in chicken. However, it has been stated in some previous reports that the first molting from the natal down feathers to the flight feathers is much earlier than that for other feather types, suggesting that flight feather formation starts as an embryonic event. The aim of this study was to determine the inception of flight feather morphogenesis and to identify embryological processes specific to flight feathers in contrast to those of down feathers.ResultsWe found that the second generation of feather that shows a flight feather-type arrangement has already started developing by chick embryonic day 18, deep in the skin of the flight feather-forming region. This was confirmed by shh gene expression that shows barb pattern, and the expression pattern revealed that the second generation of feather development in the flight feather-forming region seems to start by embryonic day 14. The first stage at which we detected a specific morphology of the feather bud in the flight feather-forming region was embryonic day 11, when internal invagination of the feather bud starts, while the external morphology of the feather bud is radial down-type.ConclusionThe morphogenesis for the flight feather, the most advanced type of feather, has been drastically modified from the beginning of feather morphogenesis, suggesting that early modification of the embryonic morphogenetic process may have played a crucial role in the morphological evolution of this key innovation. Co-optation of molecular cues for axial morphogenesis in limb skeletal development may be able to modify morphogenesis of the feather bud, giving rise to flight feather-specific morphogenesis of traits.

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Upstream regulation for initiation of restricted Shh expression in the chick limb bud

Cited by 10 publications

References 111 publications

Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development

Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development

LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development

Flight feather development: its early specialization during embryogenesis

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