Baljinder Mankoo

<p><strong>Gene Regulatory Networks in musculoskeleletal development</strong><br />A central question in developmental biology is how the onset of gene expression results in the differentiation of a multi-potential progenitor cell pool into subsets of divergent cell fates. Progenitor cells in somites differentiate in response to extracellular signals to produce skeletal muscles, muscle stem cells, cartilage, tendon, endothelial and smooth muscle cells. We are investigating how signals are integrated at the level of gene expression through Gene Regulatory Networks to produce these differential outputs. <br /><br /><strong>Somite development and differentiation </strong><br />The skeletal muscles of the trunk and limbs and the axial skelelton (ribs and vertebrae) originate in somites, which are formed, as pairs on each side of the neural tube, as distinctive blocks of mesodermal cells. The somites give rise to the trunk and limb muscles and the asscouated muscle stem cells, the cartilage of the vertebrae and ribs, the tendons associated with the vertebral column, blood vessels of the limb and the dermis.<br /><br /><strong>Muscle morphogenesis</strong><br />The limb bud is an important embryological model for studying how the patterns of cells and tissues are established. Most studies, however, have focussed on the skeletal elements of the limb and there is a paucity of knowledge of the basis of muscle and muscle connective tissue (including tendons) patterning. We use transgenic models to investigate the formation of fully defined limb muscles and associated connective tissue and tendons&nbsp;to study reciprocal molecular and cellular interactions between these distinct cell types. Our transgenic models are used to research into muscle stem cell development,&nbsp; and tendon fibroblasts and tendon stem cells&nbsp;recruitment and maintenance. We use a variety of molecular and cellular techniques, including: gene expression analysis, transgenesis, gene knockouts, microarrays, ChIP, gel shift assays, bioinformatics, explant cultures, and in vitro cell culture. <br /><br /><strong>Recent publications:</strong></p> <ul> <li>Kirilenko P, He G, Mankoo B, Mallo M, Jones R, Bobola N. (2011) Transient activation of Meox1 is an early component of the gene regulatory network downstream of Hoxa2. Mol Cell Biol. doi:10.1128/MCB.00705-10</li> <li>Perera S, Holt MR, Mankoo BS, Gautel M. (2011) Developmental regulation of MURF ubiquitin ligases and autophagy proteins nbr1, p62/SQSTM1 and LC3 during cardiac myofibril assembly and turnover. Dev Biol. 2011 351:46-61</li> <li>Otto A, Macharia R, Matsakas A, Valasek P, Mankoo BS, Patel K (2010) A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity. Dev Biol. 343:51-62</li> <li>Reijntjes S, Francis-West P, Mankoo BS (2010) Retinoic acid is both necessary for and inhibits myogenic commitment and differentiation in the chick limb. Int. J. Dev. Biol. 54:125-34</li> <li>Skuntz S, Mankoo B, Nguyen M-T, Hustert E, Nakayama A, Tournier-Lasserve E, Wright CV, Pachnis V, Bharti K, Arnheiter H (2009) Lack of the mesodermal homeodomain protein MEOX1 disrupts sclerotome polarity and leads to a remodeling of the cranio-cervical joints of the axial skeleton. Dev. Biol. 332:383-95.&nbsp;</li> <li>Plachez C, Andrews W, Liapi A, Knoell B, Drescher U, Mankoo B, Zhe L, Mambetisaeva E, Annan A, Bannister L, Parnavelas J, Richards L, and Sundaresan V (2008) Robos are required for the correct targeting of retinalganglioncell axons in the visual pathway of the brain. Mol Cell Neurosci. 37:719-30. </li> <li>Reijntjes S, Stricker S, Mankoo BS (2007) A comparative analysis of Meox1 and Meox2 in the developing somites and limbs of the chick embryo. International Journal of Developmental Biology. 51:753-9</li> <li>Jukkola T, Trokovic R, Maj P, Lamberg A, Mankoo B, Pachnis V, Savilahti H and Partanen J (2005) Meox1Cre - a mouse line expressing Cre recombinase in somitic mesoderm. Genesis 43:148-53 </li> <li>Rodrigo I, Bovolenta P, Mankoo BS, Imai K (2004) Meox homeodomain proteins are required for Bapx1 expression in the sclerotome and activate its transcription by direct binding to its promoter. Mol Cell Biol. 24:2757-66.</li> <li>Mankoo BS, Skuntz S, Harrigan I, Grigorieva E, Candia A, Wright CV, Arnheiter H, Pachnis V (2003)The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites.. Development. 130:4655-64.</li> </ul>

Gene Regulatory Networks in musculoskeletal development.

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