Welcome to the Laboratory of Molecular Embryology
Leucine rich repeat transmembrane proteins and embryogenesis.
Our current research interests involve the gene regulation, function and mechanism of action of leucine rich repeat transmembrane proteins during mouse development, focusing on their expression and function during somitogenesis/muscle formation and neural development.
This work initiated with the identification of NLRR1, a protein containing 12 extracellular leucine rich repeats, an immunoglobulin domain, a fibronectin domain and a short intracellular tail, as a gene with striking expression in a subset of the earliest embryonic myoblasts. This gene is a member of a highly conserved family containing three genes that show distinct, highly regulated expression patterns during development.
Many different multimember gene families exist in the mammalian genome that are highly conserved in sequence and secondary structure. The families differ in the number of extracellular leucine rich repeats, the presence or absence of additional fibronectin or immunoglobulin domains and the motifs present in the intracellular tail.
Recent experiments, by us and others, has shown that one of these families, the FLRTs, is a member of the FGF signalling pathway. FLRTs can stimulate FGF signalling by interacting with FGF receptors (FGFRs) and can be phosphorylated by activated FGFR. Furthermore, Ogata et al. (2007) showed FLRT3 mediates alterations in cell adhesion via internalisation of cadherin proteins. This combined with their restricted expression patterns suggest that they are important regulators of FGF signalling and/or cell adhesion during development. The similar LRRTM family is also highly regulated during mouse development and the LINGO family can interact with neurotrophin type receptors in the nervous system and has restricted embryonic expression.
These data implicate these leucine rich repeat membrane proteins as novel regulators of cell/cell signalling and/or adhesion by interaction with cell surface proteins. They are all highly expressed in the neural system and in many cases have been implicated in neuron outgrowth and synapse formation. The fact that these molecules contain an extracellular component and they can interact with and affect signalling from receptors has led to investigations into possible therapeutic roles for these proteins. Investigations into the mechanism of action and function of these molecules may provide a way to modulate the signalling pathways that they regulate which may be valuable in altering cellular function in processes like neural regeneration, muscle repair and stem cell differentiation.