Disease relevance of Chrdl1

• Although many cell lines are suitable, those most often used in genotoxicity testing (e.g. CHL, CHO, V79, human lymphocytes, L5178Y mouse lymphoma cells) are recommended [1].
• In a collaborative study organized under the JEMS MMS, nine mouse lymphoma assay (MLA) "unique positive' NTP rodent carcinogens were re-evaluated by an in vitro chromosomal aberration assay using Chinese hamster lung fibroblast cells (CHL/IU) [2].
• The carotene induced neither reverse mutation in Salmonella typhimurium TA98, TA1537, TA100, TA1535 and in Escherichia coli WP2uvrA, nor structural and numerical (polyploidy) chromosomal aberrations in the Chinese hamster fibroblast cell line (CHL) [3].

High impact information on Chrdl1

• Deep layer pyramidal neurons of CHL1-minus mice were shifted to lower laminar positions in the visual and somatosensory cortex and developed misoriented, often inverted apical dendrites [4].
• Impaired migration of CHL1-minus cortical neurons was suggested by strikingly slower rates of radial migration in cortical slices, failure to potentiate integrin-dependent haptotactic cell migration in vitro, and accumulation of migratory cells in the intermediate and ventricular/subventricular zones in vivo [4].
• We show that the neural cell recognition molecule Close Homolog of L1 (CHL1) is required for neuronal positioning and dendritic growth of pyramidal neurons in the posterior region of the developing mouse neocortex [4].
• Ectodomain shedding of the neural recognition molecule CHL1 by the metalloprotease-disintegrin ADAM8 promotes neurite outgrowth and suppresses neuronal cell death [5].
• Taken together, we propose that ADAM8 plays an important role in physiological and pathological cell interactions by a specific release of functional CHL1 from the cell surface [5].

Biological context of Chrdl1

• A novel chordin-like protein inhibitor for bone morphogenetic proteins expressed preferentially in mesenchymal cell lineages [6].
• Stable expression of COX-2 in CHL (Chang liver) cells induced proliferation, with an increase in the proportion of cells in S-phase, but no other significant changes in cell-cycle distribution [7].

Anatomical context of Chrdl1

• A novel secreted protein, CHL (for chordin-like), with significant homology to chordin, was isolated from mouse bone marrow stromal cells [6].
• Here we demonstrate that glial cells up-regulate expression of CHL1 in response to an intraorbital crush of the adult mouse optic nerve [8].
• Altered expression of CHL1 by glial cells in response to optic nerve injury and intravitreal application of fibroblast growth factor-2 [8].
• We also demonstrate that a single intravitreal application of fibroblast growth factor-2 (FGF-2) increases expression of CHL1 in retinal astrocytes and Müller cells [8].
• Elevated expression of CHL1 by glial cells in injured optic nerves and astrocytes and Müller cells in FGF-2-treated retinas suggests a role of the protein in the lesioned central nervous system [8].

Associations of Chrdl1 with chemical compounds

• Here we describe that ADAM8, a member of the family of metalloprotease disintegrins cleaves a CHL1-Fc fusion protein in vitro at two sites corresponding to release of the extracellular domain of CHL1 in fibronectin (FN) domains II (125 kDa) and V (165 kDa), inhibited by batimastat (BB-94) [5].
• Chordin-like cysteine-rich repeats (CRs) are conserved domains present in an expanding family of secreted proteins that associate with members of the TGF beta superfamily [9].
• However, there was no therapeutic gain for the combined treatment with DDP on RIF-1, with CCNU or BCNU on KHT, or with CHL on either RIF-1 or KHT [10].

Other interactions of Chrdl1

• Interestingly, the spatiotemporal expression patterns of CHL were distinct from those of chordin in many areas examined [6].

References