Biomedical subjects

Andrea Münsterberg

Publications and source records attributed to Andrea Münsterberg.

7 recordsLinked to original sources

PubMed2006

The vertebrate spalt genes in development and disease.

The spalt proteins are encoded by a family of evolutionarily conserved genes found in species as diverse as Drosophila, C. elegans and vertebrates. In humans, mutations in some of these genes are associated with several congenital disorders which underscores the importance of spalt gene function in embryonic development. Recent studies have begun to cast light on the functions of this family of proteins with increasing understanding of the developmental processes regulated and the molecular mechanisms used. Here we review what is currently known about the role of spalt genes in vertebrate development and human disease.

Animals↗

PubMed2006

FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos.

The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that regulate gene expression in metazoans. We have cloned short RNAs from chicken embryos and identified five new chicken miRNA genes. Genome analysis identified 17 new chicken miRNA genes based on sequence homology to previously characterized mouse miRNAs. Developmental Northern blots of chick embryos showed increased accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem cell-specific mir-302, which was expressed at high levels at early stages and then declined. In situ analysis of mature miRNAs revealed the restricted expression of mir-124 in the central nervous system and of mir-206 in developing somites, in particular the developing myotome. In addition, we investigated how miR-206 expression is controlled during somite development using bead implants. These experiments demonstrate that fibroblast growth factor (FGF) -mediated signaling negatively regulates the initiation of mir-206 gene expression. This may be mediated through the effects of FGF on somite differentiation. These data provide the first demonstration that developmental signaling pathways affect miRNA expression. Thus far, miRNAs have not been studied extensively in chicken embryos, and our results show that this system can complement other model organisms to investigate the regulation of many other miRNAs.

Animals↗

PubMed2005

Feedback interactions between MKP3 and ERK MAP kinase control scleraxis expression and the specification of rib progenitors in the developing chick somite.

Cells in the early vertebrate somite receive cues from surrounding tissues, which are important for their specification. A number of signalling pathways involved in somite patterning have been described extensively. By contrast, the interactions between cells from different regions within the somite are less well characterised. Here, we demonstrate that myotomally derived FGFs act through the MAPK signal transduction cascade and in particular, ERK1/2 to activate scleraxis expression in a population of mesenchymal progenitor cells in the dorsal sclerotome. We show that the levels of active, phosphorylated ERK protein in the developing somite are crucial for the expression of scleraxis and Mkp3. MKP3 is a dual specificity phosphatase and a specific antagonist of ERK MAP kinases and we demonstrate that in somites Mkp3 transcription depends on the presence of active ERK. Therefore, MKP3 and ERK MAP kinase constitute a negative feedback loop activated by FGF in sclerotomal progenitor cells. We propose that tight control of ERK signalling strength by MKP3 is important for the appropriate regulation of downstream cellular responses including the activation of scleraxis. We show that increased or decreased levels of phosphorylated ERK result in the loss of scleraxis transcripts and the loss of distal rib development, highlighting the importance of the MKP3-ERK-MAP kinase mediated feedback loop for cell specification and differentiation.

Animals↗

PubMed2005

Expression of csal1 in pre limb-bud chick embryos.

The spalt family of transcriptional repressors has been implicated in limb, heart, ear and kidney development and truncating mutations in a human gene, SALL1, result in the autosomal dominant disorder Townes-Brocks syndrome. Here we show the expression pattern of the chick orthologue of the SALL1 gene, csal1, during early development. We found csal1 expression in the heart and in the pharynx, a source of inductive signals during heart development. Expression was also seen in involuting mesoderm and later in presegmented paraxial mesoderm. We also describe expression in the ectoderm and neural plate of the early embryo and subsequent expression in the neural tube.

Animals↗

PubMed2004

Dynamic expression of Lef/Tcf family members and beta-catenin during chick gastrulation, neurulation, and early limb development.

Members of the Lef/Tcf family of HMG-box transcription factors mediate the response to Wnt as part of the canonical Wnt signaling cascade. Positive and negative cofactors, including beta-catenin, CtBP, and Smad3, regulate the activity of Lef/Tcf transcription complexes. Interaction of Lef/Tcfs with beta-catenin results in target gene activation or repression, depending on the context. Here, we report the cloning of a novel chick Tcf-1 splice variant and of a partial cDNA for chick Tcf-3. We describe their expression patterns during early development and have compared them with the expression profiles of Lef-1 and beta-catenin. We found restricted patterns during gastrulation, neurulation, somitogenesis, and early limb development. beta-catenin and Lef/Tcf expression did not always coincide, indicating developmental contexts in which Lef/Tcf proteins may interact with other cofactors and conversely, the areas in which beta-catenin may interact with other coregulators, or be involved in regulating adhesive properties of cells.

Animals↗

PubMed2003

Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome.

We have previously shown that the paired-box transcription factors Pax1 and Pax9 synergistically act in the proper formation of the vertebral column. Nevertheless, downstream events of the Pax1/Pax9 action and their target genes remain to be elucidated. We show, by analyzing Pax1;Pax9 double mutant mice, that expression of Bapx1 in the sclerotome requires the presence of Pax1 and Pax9, in a gene dose-dependent manner. By using a retroviral system to overexpress Pax1 in chick presomitic mesoderm explants, we show that Pax1 can substitute for Shh in inducing Bapx1 expression and in initiating chondrogenic differentiation. Furthermore, we demonstrate that Pax1 and Pax9 can transactivate regulatory sequences in the Bapx1 promoter and that they physically interact with the Bapx1 promoter region. These results strongly suggest that Bapx1 is a direct target of Pax1 and Pax9. Together, we conclude that Pax1 and Pax9 are required and sufficient for the chondrogenic differentiation of sclerotomal cells.

Animals↗

PubMed2002

Fin development in a cartilaginous fish and the origin of vertebrate limbs.

Recent fossil finds and experimental analysis of chick and mouse embryos highlighted the lateral fin fold theory, which suggests that two pairs of limbs in tetrapods evolved by subdivision of an elongated single fin. Here we examine fin development in embryos of the primitive cartilaginous fish, Scyliorhinus canicula (dogfish) using scanning electron microscopy and investigate expression of genes known to be involved in limb positioning, identity and patterning in higher vertebrates. Although we did not detect lateral fin folds in dogfish embryos, Engrailed-1 expression suggests that the body is compartmentalized dorso-ventrally. Furthermore, specification of limb identity occurs through the Tbx4 and Tbx5 genes, as in higher vertebrates. In contrast, unlike higher vertebrates, we did not detect Shh transcripts in dogfish fin-buds, although dHand (a gene involved in establishing Shh) is expressed. In S. canicula, the main fin axis seems to lie parallel to the body axis. 'Freeing' fins from the body axis and establishing a separate 'limb' axis has been proposed to be a crucial step in evolution of tetrapod limbs. We suggest that Shh plays a critical role in this process.

Animals↗