Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development

Bečić, Tina; Kero, Darko; Vukojević, Katarina; Mardesic, Snjezana; Saraga-Babić, Mirna

doi:10.1016/j.acthis.2018.01.008

Cited by 18 publications

(12 citation statements)

References 47 publications

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“…FGF2 is endogenously expressed in the chicken [ 11 , 17 ] and human AER [ 18 ], has broader effects than FGF4 and FGF8 [ 19 ], and interacts with greater affinity to the primary ZPA-related Fgf receptor (FGFr1cIII) [ 20 , 21 ]. Thus, we applied FGF2-laden beads to chicken limb buds to generate ZPA domain and the non-ZPA domain transcriptomes.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

confidence: 99%

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

Watson

Feenstra

Arsdale

et al. 2018

JDB

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“…MSX2 participates in the development of multiple organs, such as craniofacial tissues, limb, heart, and neural crest derivates [28][29][30]. Nagel et al reported that MSX2 was identified as a physiological NK-like subfamily of homeobox gene (NKL) involved in T cell differentiation via regulation of NOTCH3 signaling [34].…”

Section: Discussionmentioning

confidence: 99%

“…Muscle segment homeobox2 (MSX2), a homeoboxcontaining transcription factor, is implicated in organogenesis and the development processes of several types of tissues, including craniofacial tissues, limb, heart, and neural crest derivates [28][29][30]. However, whether MSX2 plays a role in hematopoietic development is still unclear.…”

Section: Introductionmentioning

confidence: 99%

MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells

Wang

et al. 2020

Stem Cell Res Ther

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Background: Strategies of generating functional blood cells from human pluripotent stem cells (hPSCs) remain largely unsuccessful due to the lack of a comprehensive understanding of hematopoietic development. Endothelialto-hematopoietic transition (EHT) serves as the pivotal mechanism for the onset of hematopoiesis and is negatively regulated by TGF-β signaling. However, little is known about the underlying details of TGF-β signaling during EHT. Methods: In this study, by applying genome-wide gene profiling, we identified muscle segment homeobox2 (MSX2) as a potential mediator of TGF-β signaling during EHT. We generated MSX2-deleted human embryonic stem cell (hESC) lines using the CRISPR/Cas9 technology and induced them to undergo hematopoietic differentiation. The role of MSX2 in hematopoiesis and functional regulation of TGFβ signaling in EHT was studied. Results: We identified MSX2 as a novel regulator of human hematopoiesis. MSX2 deletion promotes the production of hematopoietic cells from hESCs. Functional and bioinformatics studies further demonstrated that MSX2 deletion augments hematopoietic differentiation of hESCs by facilitating EHT. Mechanistically, MSX2 acts as a downstream target of TGFβ signaling to mediate its function during EHT. Conclusions: Our results not only improve the understanding of EHT, but may also provide novel insight into the efficient production of functional blood cells from hPSCs for regenerative medicine.

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“…Among them, FGF‐1 subfamily (including FGF‐1 and FGF‐2), FGF‐4 subfamily (including FGF‐4, FGF‐5 and FGF‐6), FGF‐7 subfamily (including FGF‐3, FGF‐7, FGF‐10 and FGF‐22), FGF‐8 subfamily (including FGF‐8, FGF‐17 and FGF‐18), FGF‐9 subfamily (including FGF‐9, FGF‐16 and FGF‐20) and FGF‐11 subfamily (including FGF‐11–14) belong to paracrine class, while FGF‐19 subfamily (including FGF‐19, FGF‐21 and FGF‐23) belong to the endocrine category 8–11 . Current studies have shown that FGF members, such as FGF‐2, FGF‐9, FGF‐18 and FGF‐19, have been closely implicated into the physiology and pathology of cartilage and they can promote the development of cartilage and bone, 1,9,12–16 but the specific role of FGF‐8 subfamily in the growth and development of cartilage and cartilage disease progression remains partially known. The FGF‐8 subfamily consists of three proteins: FGF‐8, FGF‐17 and FGF‐18 9,12 .…”

Section: Introductionmentioning

confidence: 99%

The role of fibroblast growth factor 8 in cartilage development and disease

Chen

Cui

Zhang

et al. 2022

J Cellular Molecular Medi

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Fibroblast growth factor 8 (FGF‐8), also known as androgen‐induced growth factor (AIGF), is presumed to be a potent mitogenic cytokine that plays important roles in early embryonic development, brain formation and limb development. In the bone environment, FGF‐8 produced or received by chondrocyte precursor cells binds to fibroblast growth factor receptor (FGFR), causing different levels of activation of downstream signalling pathways, such as phospholipase C gamma (PLCγ)/Ca2+, RAS/mitogen‐activated protein kinase‐extracellular regulated protein kinases (RAS/MAPK‐MEK‐ERK), and Wnt‐β‐catenin‐Axin2 signalling, and ultimately controlling chondrocyte proliferation, differentiation, cell survival and migration. However, the molecular mechanism of FGF‐8 in normal or pathological cartilage remains unclear, and thus, FGF‐8 represents a novel exploratory target for studies of chondrocyte development and cartilage disease progression. In this review, studies assessing the relationship between FGF‐8 and chondrocytes that have been published in the past 5 years are systematically summarized to determine the probable mechanism and physiological effect of FGF‐8 on chondrocytes. Based on the existing research results, a therapeutic regimen targeting FGF‐8 is proposed to explore the possibility of treating chondrocyte‐related diseases.

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Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development

Cited by 18 publications

References 47 publications

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

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

MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells

The role of fibroblast growth factor 8 in cartilage development and disease

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