Disease relevance of Celsr1

• Failure of neural tube closure is one of the most common human birth defects, and a murine flamingo (fmi) homologue, Celsr1/fmi-1, was identified as the defective gene in two mouse mutants exhibiting failure of closure 1 of the neural tube [1].
• Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse [2].

High impact information on Celsr1

• We show that these mutants, spin cycle and crash, carry independent missense mutations within the coding region of Celsr1, encoding a large protocadherin molecule [1] [2].
• The identification of mouse mutants of Celsr1 provides the first evidence for the function of the Celsr family in planar cell polarity in mammals and further supports the involvement of a planar cell polarity pathway in vertebrate neurulation [2].
• Here, we report the results of our study of its embryonic and postnatal expression patterns together with those of two other paralogs, Celsr1 and Celsr3 [3].
• Celsr1 and Celsr2 expression is observed during gastrulation and within the developing nervous system [4].
• Homologous genes have been identified in C. elegans and D. melanogaster suggesting that the Celsr gene family is ancient. mCelsr1 mRNA expression precedes gastrulation, is subsequently restricted primarily to ectodermal derivatives and is tightly regulated in the developing central nervous system (CNS) [5].

Biological context of Celsr1

• The flamingo-related mouse Celsr family (Celsr1-3) genes exhibit distinct patterns of expression during embryonic development [4].
• Celsr1, a neural-specific gene encoding an unusual seven-pass transmembrane receptor, maps to mouse chromosome 15 and human chromosome 22qter [6].
• We report that Celsr1 maps to proximal mouse Chromosome 15 and human chromosome 22qter, a region of conserved synteny [6].
• The European Collaborative Interspecific Backcross (EUCIB) and BXD recombinant inbred strains were used for mapping Celsr1 cDNA clones in the mouse, and fluorescence in situ hybridization was used to map human Celsr1 cosmid clones on metaphase chromosomes [6].

Anatomical context of Celsr1

• The results presented here extend our previous finding of expression of the Celsr1 receptor in the embryo and show that expression continues into adult life when expression in the brain is localized principally in the ependymal cell layer, choroid plexus, and the area postrema [6].

Analytical, diagnostic and therapeutic context of Celsr1

• Reverse transcriptase-polymerase chain reaction analysis and in situ hybridization were used to determine the spatial restriction of Celsr1 transcripts in adult and embryonic mice [6].

References