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Fernanda Bajanca

Publications and source records attributed to Fernanda Bajanca.

7 recordsLinked to original sources
PubMed2006

Progressive mRNA decay establishes an mkp3 expression gradient in the chick limb bud.

The apical ectodermal ridge (AER) controls limb outgrowth and patterning, such that its removal causes changes in mesodermal gene expression, cell death and limb truncation. Fibroblast growth factor (FGF) family members are expressed in the AER and can rescue limb bud outgrowth after AER removal. Cells localized underneath the AER are maintained in an undifferentiated state by the FGFs produced by the AER. MAPK phosphatase 3 (mkp3) is a downstream effector of FGF8 signalling during limb bud development and is expressed in the distal limb mesenchyme. The present work evidences a gradient of mkp3 transcripts along the chick limb bud, in a distal to proximal direction. mkp3 transcription occurs only in the most distal limb bud cells and its mRNA gradient throughout the limb results from progressive mRNA decay. We show that FGF8-soaked beads induce ectopic mkp3 expression, indicating that AER-derived FGF8 protein may activate mkp3 in the distal mesenchyme.

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PubMed2006

Integrin alpha6beta1-laminin interactions regulate early myotome formation in the mouse embryo.

We addressed the potential role of cell-laminin interactions during epaxial myotome formation in the mouse embryo. Assembly of the myotomal laminin matrix occurs as epaxial myogenic precursor cells enter the myotome. Most Myf5-positive and myogenin-negative myogenic precursor cells localise near assembled laminin, while myogenin-expressing cells are located either away from this matrix or in areas where it is being assembled. In Myf5(nlacZ/nlacZ) (Myf5-null) embryos, laminin, collagen type IV and perlecan are present extracellularly near myogenic precursor cells, but do not form a basement membrane and cells are not contained in the myotomal compartment. Unlike wild-type myogenic precursor cells, Myf5-null cells do not express the alpha6beta1 integrin, a laminin receptor, suggesting that integrin alpha6beta1-laminin interactions are required for myotomal laminin matrix assembly. Blocking alpha6beta1-laminin binding in cultured wild-type mouse embryo explants resulted in dispersion of Myf5-positive cells, a phenotype also seen in Myf5(nlacZ/nlacZ) embryos. Furthermore, inhibition of alpha6beta1 resulted in an increase in Myf5 protein and ectopic myogenin expression in dermomyotomal cells, suggesting that alpha6beta1-laminin interactions normally repress myogenesis in the dermomyotome. We conclude that Myf5 is required for maintaining alpha6beta1 expression on myogenic precursor cells, and that alpha6beta1 is necessary for myotomal laminin matrix assembly and cell guidance into the myotome. Engagement of laminin by alpha6beta1 also plays a role in maintaining the undifferentiated state of cells in the dermomyotome prior to their entry into the myotome.

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PubMed2005

Integrin repertoire on myogenic cells changes during the course of primary myogenesis in the mouse.

Cells interact with the extracellular matrix through receptors, most commonly of the integrin family. We (Cachaco et al. [2003] Development 130:1659-1671) and others (Schwander et al. [2003] Dev. Cell 4:673-685) have demonstrated a role for beta1 integrins in mouse primary myogenesis. However, it is unclear what alpha subunits pair with beta1 during this process in vivo. Here, we determined alpha subunit expression patterns at embryonic day (E) 11.5-E14.5. Differentiated myotomal myocytes express all alpha subunits studied. As the muscle masses form both in trunk (E12.5) and limbs (E11.5-E12.5), laminin receptors alpha6beta1 and alpha7beta1 are undetectable, and an assembled laminin matrix is absent. Instead alpha1beta1, alpha4beta1, alpha5beta1, and an alpha v-containing integrin are expressed and unassembled laminin and fibronectin are abundant around myogenic cells. At E13.5-E14.5, alpha6beta1 and alpha7beta1 are expressed, and a laminin matrix forms around individual myotubes. Thus, myogenic cells change their integrin expression pattern during the course of primary myogenesis in the mouse, suggesting different roles for fibronectin- and laminin-containing matrices in this process.

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PubMed2004

Integrins in the mouse myotome: developmental changes and differences between the epaxial and hypaxial lineage.

Integrins are cellular adhesion receptors that mediate signaling and play key roles in the development of multicellular organisms. However, their role in the cellular events leading to myotome formation is completely unknown. Here, we describe the expression patterns of the alpha1, alpha4, alpha5, alpha6, and alpha7 integrin subunits in the mouse myotome and correlate them with the expression of several differentiation markers. Our results indicate that these integrin subunits may be differentially involved in the various phases of myogenic determination and differentiation. A detailed characterization of the myogenic cell types expressing the alpha4 and alpha6 subunits showed a regionalization of the myotome and dermomyotome based on cell-adhesion properties. We conclude that alpha6beta1 may be an early marker of epaxial myogenic progenitor cells. In contrast, alpha4beta1 is up-regulated in the intercalated myotome after myocyte differentiation. Furthermore, alpha4beta1 is expressed in the hypaxial dermomyotome and is maintained by early hypaxial myogenic progenitor cells colonizing the myotome.

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PubMed2003

Knock-in of integrin beta 1D affects primary but not secondary myogenesis in mice.

Integrins are extracellular matrix receptors composed of alpha and beta subunits involved in cell adhesion, migration and signal transduction. The beta1 subunit has two isoforms, beta 1A ubiquitously expressed and beta 1D restricted to striated muscle. They are not functionally equivalent. Replacement of beta 1A by beta 1D (beta 1D knock-in) in the mouse leads to midgestation lethality on a 50% Ola/50% FVB background [Baudoin, C., Goumans, M. J., Mummery, C. and Sonnenberg, A. (1998). Genes Dev. 12, 1202-1216]. We crossed the beta 1D knock-in line into a less penetrant genetic background. This led to an attenuation of the midgestation lethality and revealed a second period of lethality around birth. Midgestation death was apparently not caused by failure in cell migration, but rather by abnormal placentation. The beta 1D knock-in embryos that survived midgestation developed until birth, but exhibited severely reduced skeletal muscle mass. Quantification of myotube numbers showed that substitution of beta 1A with beta 1D impairs primary myogenesis with no direct effect on secondary myogenesis. Furthermore, long-term primary myotube survival was affected in beta 1D knock-in embryos. Finally, overexpression of beta 1D in C2C12 cells impaired myotube formation while overexpression of beta 1A primarily affected myotube maturation. Together these results demonstrate for the first time distinct roles for beta1 integrins in primary versus secondary myogenesis and that the beta 1A and beta 1D variants are not functionally equivalent in this process.

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PubMed2002

Integrin expression patterns during early limb muscle development in the mouse.

Cell-extracellular matrix interactions play crucial roles in limb muscle development but practically nothing is known on what integrins are involved before the differentiation of muscle precursor cells (MPCs) in the limb muscle masses. In this study we determine the expression patterns of integrins during early forelimb muscle development in the mouse. alpha6beta1 integrin is downregulated in the lateral dermomyotome when delamination of MPCs occurs. In late E9.5 embryos, alpha1beta1 and alpha5beta1 are expressed in a pattern very similar to pax3, which marks MPCs migrating to the limb bud. After myf5 upregulation in the limb bud, alpha1beta1 and alpha5beta1 expression is maintained and the alpha4beta1 integrin starts being expressed.

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PubMed2002

Integrin expression patterns during early limb muscle development in the mouse.

Cell-extracellular matrix interactions play crucial roles in limb muscle development but practically nothing is known on what integrins are involved before the differentiation of muscle precursor cells (MPCs) in the limb muscle masses. In this study we determine the expression patterns of integrins during early forelimb muscle development in the mouse. alpha6beta1 integrin is downregulated in the lateral dermomyotome when delamination of MPCs occurs. In late E9.5 embryos, alpha1beta1 and alpha5beta1 are expressed in a pattern very similar to pax3, which marks MPCs migrating to the limb bud. After myf5 upregulation in the limb bud, alpha1beta1 and alpha5beta1 expression is maintained and the alpha4beta1 integrin starts being expressed.

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