The novel type I serine–threonine kinase receptor Alk8 binds TGF-β in the presence of TGF-βRII

Caestecker, Mark P. de; Bottomley, M J; Bhattacharyya, Somnath; Payne, T.; Roberts, Anita B.; Yelick, Pamela C.

doi:10.1016/s0006-291x(02)00424-2

Cited by 9 publications

(13 citation statements)

References 26 publications

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“…Laf/alk8 mutants also exhibit a more severe tooth defect, exhibiting only two small teeth at this stage, whereas snh/bmp7 mutants have two fully sized teeth. These results are consistent with the possibility that Alk8 is a receptor for Bmp7 as well as for other TGF-beta family member ligands (Payne et al, 2001a;DeCaestecker et al, 2002).…”

Section: Perturbed Alk8 Expression Results In An Ap Gradient Of Defecsupporting

confidence: 89%

“…Because Alk8 gradients affect patterning of the hindbrain and corresponding neural crest streams, it is likely that Alk8 signals affect FGF, Wnt, RA, and/or Notch/Delta signaling pathways. We have demonstrated previously that Alk8 binds TGF␤ in the presence of TGF␤RII (DeCaestecker et al, 2002), and hypothesize that Alk8 may function as a BMP-TGF␤ cross-talking molecule. Experiments are ongoing to determine how altered Alk8 impacts other signaling networks and to characterize Alk8 downstream signaling partners.…”

Section: Alk8/bmp Levels Mediate Pharyngeal Arch Cartilage Growth Andmentioning

confidence: 81%

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Alk8 is required for neural crest cell formation and development of pharyngeal arch cartilages

Payne-Ferreira¹,

Yelick²

2003

Developmental Dynamics

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The type I TGF␤ family member receptor alk8 acts in bone morphogenetic protein (BMP) signaling pathways to establish dorsoventral patterning in the early zebrafish embryo. Here, we present evidence that alk8 is required for neural crest cell (NCC) formation and that alk8 signaling gradients direct the proper patterning of premigratory NCCs. We extend our previous functional studies of alk8 to demonstrate that ectopic expression of constitutively active and dominant negative Alk8, consistently results in more medially or laterally positioned premigratory NCCs, respectively. We also demonstrate that patterning defects in premigratory NCCs, induced by alk8 misexpression, correlate with subsequent defects in NCC-derived pharyngeal arch cartilages. Furthermore, an anteroposterior effect is revealed, where overexpression of Alk8 more severely affects anterior arch cartilages and decreased Alk8 activity more severely affects posterior arch cartilage formation. Ectopic expression studies of alk8 are supported by analyses of zygotic and maternal-zygotic laf/alk8 mutants and of several BMP pathway mutants. Pharyngeal mesodermal and endodermal defects in laf/alk8 mutants suggest additional roles for alk8 in patterning of these tissues. Our results provide insight into alk8-mediated BMP signaling gradients and the establishment of premigratory NCC mediolateral positioning, and extend the model for BMP patterning of the neural crest to include that of NCC-derived pharyngeal arch cartilages. Developmental Dynamics 228:683-696, 2003.

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Section: Perturbed Alk8 Expression Results In An Ap Gradient Of Defecsupporting

confidence: 89%

Section: Alk8/bmp Levels Mediate Pharyngeal Arch Cartilage Growth Andmentioning

confidence: 81%

Alk8 is required for neural crest cell formation and development of pharyngeal arch cartilages

Payne-Ferreira¹,

Yelick²

2003

Developmental Dynamics

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“…Zebrafish ef-1a appears to be present at a constant level during all the developmental stages examined. To further confirm the RT-PCR data, we performed real-time RT-PCR to compare the amounts of the three transcripts described above during the developmental stages (0, 4,8,10,16,24,30,36,48,72 and 144 hpf). Assuming the level at 24 hpf was 1, we observed that expression of bram1 was significant before gastrulation and declined during the gastrulation and somitogenesis stages (Figure 3b).…”

Section: Expression Of the Zebrafish Bram1 Genementioning

confidence: 99%

“…At 48 and 72 hpf, decreased bram1 expression was evident throughout the brain (Figure 4g, h). It worths noting that the expression pattern of bmp receptor is overlapping with the expression pattern of zebrafish bram1 [25][26][27][28][29][30].…”

Section: Spatiotemporal Expression Pattern Of the Zebrafish Bram1 Genementioning

confidence: 99%

Molecular cloning, expression and characterization of the zebrafish bram1 gene, a BMP receptor-associated molecule

Wu¹,

Huang

Hwang

et al. 2006

J Biomed Sci

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We have identified a cDNA clone encoding BMP receptor-associated molecule 1 (BRAM1) from the zebrafish expressed sequence tag (EST) database. The 2606 bp full-length bram1 cDNA was cloned, and further confirmed by nucleotide sequencing. The zebrafish sequence encodes a protein of 195 amino acids with an evolutionarily conserved MYND domain, which displays approximately approximately 98% homology with human and mouse BRAM1, and approximately approximately 64% homology with C. elegans BRA-1 and BRA-2. The bram1 gene, composed of five exons and four introns, spans approximately approximately 14 kb on linkage group 14 of the zebrafish genome. RT-PCR and whole mount in situ hybridization analyses disclosed that zebrafish BRAM1 is a maternal factor. The protein interacts directly with zebrafish BMP Receptor type IA, as observed from GST-pull down and co-immunoprecipitation assays. Furthermore, cotransfection of zebrafish BRAM1 with the corresponding BMP receptor resulted in down-regulation of BMP-mediated signaling. Our results collectively indicate that BRAM1 plays a biological role during zebrafish development.

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“…Analyses of zebrafish expressing constitutively active and dominant negative Alk8 isoforms [Payne et al, 2001a, b], and of the alk8 mutant lost-a-fin [Bauer et al, 2001;Mintzer et al, 2001;Payne and Yelick, 2003] demonstrate requirements for alk8 in neural crest cell specification and patterning [Payne and Yelick, 2003], and in craniofacial pharyngeal arch cartilage and tooth development [Payne et al, 2001a, b]. Alk8 functions in both Bmp [Bauer et al, 2001;Mintzer et al, 2001;Payne and Yelick, 2003] and in TGF-ß signaling pathways [De Caestecker et al, 2002] in establishing early dorsoventral patterning of the early embryo, and in the later patterning of neural crest cell-derived pharyngeal arch cartilages [Payne and Yelick, 2003].…”

Section: Transforming Growth Factor-ß Family Member Signaling and Cramentioning

confidence: 99%

Immunolocalization of Alk8 during Replacement Tooth Development in Zebrafish

Perrino¹,

Yelick²

2004

Cells Tissues Organs

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The novel type I transforming growth factor-β (TGF-β) family member receptor Alk8 was previously identified in a degenerate RT-PCR screen for zebrafish type I and II TGF-β family member receptors. Functional analyses revealed that Alk8 acts through Bmp signaling pathways in early embryonic dorsoventral patterning, in neural crest cell specification, and in patterning and differentiation of neural crest cell-derived pharyngeal arch cartilages. In addition, Alk8 forms active signaling complexes with TGF-β1 and the TGF-β RII receptor, suggesting that Alk8 mediates cross talk between Bmp and TGF-β subfamily members. In this study, immunohistochemical analysis was performed on zebrafish aged 2 days postfertilization to 1 year, revealing immunolocalization of Alk8 to tissues of the tooth-bearing ceratobranchial 5 (cb5) arch including dental epithelial and mesenchymal tooth tissues of developing primary and replacement teeth, mucous-producing crypt epithelium, keratinized bite plate, and developing taste buds. These results suggest roles for Alk8 in patterning tooth-bearing pharyngeal epithelium, in the initiation of tooth development, in odontoblast and ameloblast differentiation, and in osteoblast maturation. The ability for zebrafish to continuously form teeth throughout their lives allows for the comparison of Alk8 expression in both primary and replacement tooth development, revealing identical Alk8 expression profiles. This study advances our current understanding of the functions of Alk8, particularly with respect to primary and replacement tooth formation, reveals additional roles for Alk8 in dental epithelial patterning and in odontoblast, ameloblast and osteoblast differentiation, and demonstrates the utility of the zebrafish as a model for primary and replacement tooth development.

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The novel type I serine–threonine kinase receptor Alk8 binds TGF-β in the presence of TGF-βRII

Cited by 9 publications

References 26 publications

Alk8 is required for neural crest cell formation and development of pharyngeal arch cartilages

Alk8 is required for neural crest cell formation and development of pharyngeal arch cartilages

Molecular cloning, expression and characterization of the zebrafish bram1 gene, a BMP receptor-associated molecule

Immunolocalization of Alk8 during Replacement Tooth Development in Zebrafish

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