A gene expression map of human chromosome 21 orthologues in the mouse.

The DNA sequence of human chromosome 21 (HSA21) has opened the route for a systematic molecular characterization of all of its genes. Trisomy 21 is associated with Down's syndrome, the most common genetic cause of mental retardation in humans. The phenotype includes various organ dysmorphies, stereotypic craniofacial anomalies and brain malformations. Molecular analysis of congenital aneuploidies poses a particular challenge because the aneuploid region contains many protein-coding genes whose function is unknown. One essential step towards understanding their function is to analyse mRNA expression patterns at key stages of organism development. Seminal works in flies, frogs and mice showed that genes whose expression is restricted spatially and/or temporally are often linked with specific ontogenic processes. Here we describe expression profiles of mouse orthologues to HSA21 genes by a combination of large-scale mRNA in situ hybridization at critical stages of embryonic and brain development and in silico (computed) mining of expressed sequence tags. This chromosome-scale expression annotation associates many of the genes tested with a potential biological role and suggests candidates for the pathogenesis of Down's syndrome.

A mouse gene of the paired-related homeobox class expressed in the caudal somite compartment and in the developing vertebral column, kidney and nervous system.

During vertebrate embryonic development, pairs of metameric units, the somites, bud off at the cranial end of the paraxial mesoderm. The somites soon obtain cranio-caudal and dorso-ventral polarity. Establishment of dorso-ventral and medio-lateral polarity depends on multiple signals from the notochord, neural tube surface ectoderm and lateral mesoderm. The establishment of cranio-caudal polarity in the somite is less well understood. One molecule involved is the Dll1 gene product, a transmembrane protein expressed in the unsegmented paraxial mesoderm and in the caudal half of the somites. We have identified a gene, Uncx4.1, expressed in the caudal half of newly formed somites. It encodes a protein belonging to the paired-related class of homeodomain transcription factors. Uncx4.1 expression is first detected in the entire caudal half of the somites, is later down-regulated in the myotome and dermatome, and is maintained in the caudal sclerotome and its derivatives from which part of the vertebral column will form. Thus, Uncx4.1 may be involved in the establishment and maintenance of segment polarity and in vertebral column formation. Uncx4.1 is also expressed in the first branchial arch, the meso- and metanephric kidney, the central nervous system and the first digit of the forelimb, suggesting control functions of Uncx4.1 in multiple processes of embryogenesis.