BMP signaling is required for nkx2.3-positive pharyngeal pouch progenitor specification in zebrafish

Li, Linwei; Guan, Ning; Yang, Songbai; Yan, Yan; Cao, Yu; Wang, Qiang

doi:10.1371/journal.pgen.1007996

Cited by 20 publications

(27 citation statements)

References 65 publications

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“…Firstly, morphogenesis and neurogenesis of epibranchial placodes depend on signals produced by intact pharyngeal pouches (Ladher et al, 2010). Secondly, in zebrafish, FGF and BMP signaling promote pharyngeal pouch formation (Crump et al, 2004;Nechiporuk et al, 2005;Lovely et al, 2016;Li et al, 2019). Thirdly, pharyngeal pouches 3 and 4 are malformed in Fgf8 hypomorphic mice (Abu-Issa et al, 2002;Frank et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

Washausen

Knabe

2021

Front. Cell Dev. Biol.

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Placodes are ectodermal thickenings of the embryonic vertebrate head. Their descendants contribute to sensory organ development, but also give rise to sensory neurons of the cranial nerves. In mammals, the signaling pathways which regulate the morphogenesis and neurogenesis of epibranchial placodes, localized dorsocaudally to the pharyngeal clefts, are poorly understood. Therefore, we performed mouse whole embryo culture experiments to assess the impact of pan-fibroblast growth factor receptor (FGFR) inhibitors, anti-FGFR3 neutralizing antibodies or the pan-bone morphogenetic protein receptor (BMPR) inhibitor LDN193189 on epibranchial development. We demonstrate that each of the three paired epibranchial placodes is regulated by a unique combination of FGF and/or bone morphogenetic protein (BMP) signaling. Thus, neurogenesis depends on fibroblast growth factor (FGF) signals, albeit to different degrees, in all epibranchial placodes (EP), whereas only EP1 and EP3 significantly rely on neurogenic BMP signals. Furthermore, individual epibranchial placodes vary in the extent to which FGF and/or BMP signals (1) have access to certain receptor subtypes, (2) affect the production of Neurogenin (Ngn)2+ and/or Ngn1+ neuroblasts, and (3) regulate either neurogenesis alone or together with structural maintenance. In EP2 and EP3, all FGF-dependent production of Ngn2+ neuroblasts is mediated via FGFR3 whereas, in EP1, it depends on FGFR1 and FGFR3. Differently, production of FGF-dependent Ngn1+ neuroblasts almost completely depends on FGFR3 in EP1 and EP2, but not in EP3. Finally, FGF signals turned out to be responsible for the maintenance of both placodal thickening and neurogenesis in all epibranchial placodes, whereas administration of the pan-BMPR inhibitor, apart from its negative neurogenic effects in EP1 and EP3, causes only decreases in the thickness of EP3. Experimentally applied inhibitors most probably not only blocked receptors in the epibranchial placodes, but also endodermal receptors in the pharyngeal pouches, which act as epibranchial signaling centers. While high doses of pan-FGFR inhibitors impaired the development of all pharyngeal pouches, high doses of the pan-BMPR inhibitor negatively affected only the pharyngeal pouches 3 and 4. In combination with partly concordant, partly divergent findings in other vertebrate classes our observations open up new approaches for research into the complex regulation of neurogenic placode development.

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Section: Resultsmentioning

confidence: 99%

Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

Washausen

Knabe

2021

Front. Cell Dev. Biol.

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“…To explore which BMP ligands are specifically required for PAA progenitor specification, knockdown experiments were performed using previously validated antisense MOs targeting bmp2a , bmp2b , bmp4 and bmp5 ( Chocron et al, 2007 ; Li et al, 2019 ; Naye et al, 2012 ; Shih et al, 2017 ). As expected, injection of these MOs into wild-type embryos caused clear defects in the development of the hepatic bud, pharyngeal pouches, presumptive cloaca and neural crest cells, respectively ( …”

Section: Resultsmentioning

confidence: 99%

“…6 A,A′). We have previously reported that bmp2b is essential for pharyngeal pouch progenitor specification ( Li et al, 2019 ). In fact, bmp2b morphants showed no pharyngeal pouches at 36 hpf, as indicated by the expression of the pouch epithelium marker nkx2.3 ( …”

Section: Resultsmentioning

confidence: 99%

“…Morpholino oligonucleotides (MOs) were purchased from Gene Tools. The standard control MO (5′-CCTCTTACCTCAGTTACAATTTATA-3′) ( Dickmeis et al, 2001 ), sox32 MO (5′-CAGGGAGCATCCGGTCGAGATACAT-3′) ( Dickmeis et al, 2001 ), bmp2a MO (5′-AGTAAACACTTGCTTACCATCATGG-3′) ( Naye et al, 2012 ), bmp2b MO (5′-CGCGGACCACGGCGACCATGATC-3′) ( Li et al, 2019 ), bmp4 MO (5′-GTCTCGACAGAAAATAAAGCATGGG-3′) ( Chocron et al, 2007 ), bmp5 MO (5′-TTGACCAGGATGATGATGCTTTCAG-3′) ( Shih et al, 2017 ) and nkx2.5 MO (5′-TGTCAAGGCTCACCTTTTTTCTCTT-3′) ( Paffett-Lugassy et al, 2013 ) were used as previously described. All the MOs were injected at one-cell stage into zebrafish embryos.…”

Section: Methodsmentioning

confidence: 99%

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Pharyngeal pouches provide a niche microenvironment for arch artery progenitor specification

Mao

Zhang

et al. 2020

Development

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The paired pharyngeal arch arteries (PAAs) are transient blood vessels connecting the heart with the dorsal aorta during embryogenesis. Although PAA malformations often occur along with pharyngeal pouch defects, the functional interaction between these adjacent tissues remains largely unclear. Here, we report that pharyngeal pouches are essential for PAA progenitor specification in zebrafish embryos. We reveal that the segmentation of pharyngeal pouches coincides spatiotemporally with the emergence of PAA progenitor clusters. These pouches physically associate with pharyngeal mesoderm in discrete regions and provide a niche microenvironment for PAA progenitor commitment by expressing BMP proteins. Specifically, pouch-derived BMP2a and BMP5 are the primary niche cues responsible for activating the BMP/Smad pathway in pharyngeal mesoderm, thereby promoting progenitor specification. In addition, BMP2a and BMP5 play an inductive function in the expression of the cloche gene npas4l in PAA progenitors. cloche mutants exhibit a striking failure to specify PAA progenitors and display ectopic expression of head muscle markers in the pharyngeal mesoderm. Therefore, our results support a crucial role for pharyngeal pouches in establishing a progenitor niche for PAA morphogenesis via BMP2a/5 expression.

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“…BMP signaling regulates cranial neural crest cell proliferation, apoptosis, patterning, growth, morphogenesis, and chondrogenic differentiation during craniofacial development [31,34,41]. It is also required for the specification of pharyngeal pouch progenitors which are essential for craniofacial skeleton formation [56]. Defects in BMP signaling are associated with cleft lip/palate in mice and human [57,58].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Signaling Regulates Craniofacial Cartilage Development in Zebrafish

Kwon

2019

JDB

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Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D functions through the vitamin D receptor (VDR). A hereditary vitamin-D-resistant rickets with facial dysmorphism has been reported, but the involvement of VDR signaling during early stages of craniofacial development remains to be elucidated. The present study investigated whether VDR signaling is implicated in zebrafish craniofacial cartilage development using a morpholino-based knockdown approach. Two paralogous VDR genes, vdra and vdrb, have been found in zebrafish embryos. Loss-of-vdra has no discernible effect on cartilage elements, whereas loss-of-vdrb causes reduction and malformation of craniofacial cartilages. Disrupting both vdra and vdrb leads to more severe defects or complete loss of cartilage. Notably, knockdown of vdrb results in elevated expression of follistatin a (fsta), a bone morphogenetic protein (BMP) antagonist, in the adjacent pharyngeal endoderm. Taken together, these findings strongly indicate that VDR signaling is required for early craniofacial cartilage development in zebrafish.

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BMP signaling is required for nkx2.3-positive pharyngeal pouch progenitor specification in zebrafish

Cited by 20 publications

References 65 publications

Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

Pharyngeal pouches provide a niche microenvironment for arch artery progenitor specification

Vitamin D Receptor Signaling Regulates Craniofacial Cartilage Development in Zebrafish

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