User talk:PatrickTam

Impact of WNT signaling on tissue lineage differentiation in the early mouse embryo

Dev Growth Differ. 2011 Jul 15. doi: 10.1111/j.1440-169X.2011.01292.x. [Epub ahead of print]

Tanaka SS, Kojima Y, Yamaguchi YL, Nishinakamura R, Tam PP. Source Department of Kidney Development, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, Japan Embryology Unit, Children's Medical Research Institute (CMRI), Westmead, NSW, Australia Global COE "Cell Fate Regulation Research and Education Unit", Kumamoto University, Kumamoto, Japan Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.

Abstract

WNT signaling activity is involved in the regulation of many cellular functions, including proliferation, migration, cell fate specification, maintenance of pluripotency and induction of tumorigenicity. Here we summarize recent progress towards understanding the regulation of canonical WNT/β-catenin signaling activity through feedback regulatory loops involving the ligands, agonists and antagonists, the availability of intracellular pools of active β-catenin and the cross-regulation of the WNT activity by β-catenin independent pathway. We also review recent findings on the role of WNT/β-catenin signaling in tissue lineage differentiation during embryogenesis and the maintenance and self renewal of embryo-derived stem cells in vitro.

PMID 21762130

A novel transcript of cyclin-dependent kinase-like 5 (CDKL5) has an alternative C-terminus and is the predominant transcript in brain

Hum Genet. 2011 Jul 12. [Epub ahead of print]

Williamson SL, Giudici L, Kilstrup-Nielsen C, Gold W, Pelka GJ, Tam PP, Grimm A, Prodi D, Landsberger N, Christodoulou J. Source NSW Centre for Rett Syndrome Research, The Children's Hospital at Westmead, Sydney, NSW, 2145, Australia.

Abstract

The X-linked cyclin-dependent kinase-like 5 (CDKL5) gene is an important molecular determinant of early-onset intractable seizures with infantile spasms and Rett syndrome-like phenotype. The gene encodes a kinase that may influence components of molecular pathways associated with MeCP2. In humans there are two previously reported splice variants that differ in the 5' untranslated exons and produce the same 115 kDa protein. Furthermore, very recently, a novel transcript including a novel exon (16b) has been described. By aligning both the human and mouse CDKL5 proteins to the orthologs of other species, we identified a theoretical 107 kDa isoform with an alternative C-terminus that terminates in intron 18. In human brain and all other tissues investigated except the testis, this novel isoform is the major CDKL5 transcript. The detailed characterisation of this novel isoform of CDKL5 reveals functional and subcellular localisation attributes that overlap greatly, but not completely, with that of the previously studied human CDKL5 protein. Considering its predominant expression in the human and mouse brain, we believe that this novel isoform is likely to be of primary pathogenic importance in human diseases associated with CDKL5 deficiency, and suggest that screening of the related intronic sequence should be included in the molecular genetic analyses of patients with a suggestive clinical phenotype.

PMID 21748340