A Drosophila homolog of the fibroblast growth factor (FGF) receptor was isolated and structurally characterized. After EMS mutagenesis or imprecise excisions of marked P elements inserted upstream to the gene, a phenotypic series of mutations in the locus was isolated. The mutants exhibit defects in the two embryonic tissues in which the receptor is expressed: the tracheal system and the midline. The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits. Hypomorphic alleles exhibit partial migration of all tracheal branches; thus, the locus was termed breathless (btl). In the midline of the mutant embryos, the posterior pair of midline glial cells begins to migrate anteriorly, but fails to reach the posterior commissure. Abnormalities in cell migration appear to be a common denominator for the btl defects in these two disparate tissues. In hypomorphic mutants the cells exhibit partial migration but follow the normal tracts, suggesting that the presence of this receptor is essential for the ability of the migrating cells to recognize external guiding cues.

The Drosophila homolog of the vertebrate fibroblast growth factor receptor (FGF-R) was isolated by low-stringency hybridization. In contrast to the diversity of this subclass of receptor tyrosine kinases in vertebrates, the Drosophila genome appears to encode only a single homolog. Nucleotide sequence analysis demonstrates that the Drosophila FGF-R homolog (DFGF-R) protein has a conserved sequence, size, and organization. The extracellular region encodes three immunoglobulin-like domains, and the cytoplasmic kinase domain exhibits a high degree of similarity to the vertebrate FGF-Rs with the typical split kinase and comparably sized juxtamembrane and carboxy-terminal regions. The DFGF-R was mapped to position 70C on the third chromosome, and two overlapping chromosomal deficiencies that remove the gene were identified. Developmental Northern blots show that the gene has a single transcript of 4.3 kb and is expressed at all stages of development. Localization of the transcript and protein in embryos has shown that the gene is predominantly expressed in a restricted set of tissues: the developing tracheal system and the delaminating midline glial and neural cells. In embryos homozygous for a deletion of several genes including the DFGF-R locus, the initial formation of the tracheal pits is not affected. However, the extension of tracheal cell processes leading to the formation of the elaborate tree structure is blocked. The DFGF-R protein may thus participate in receiving spatial cues that guide tracheal cell outgrowth.

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We isolated and determined the sequences oftwo human germ-line heavy chain variable region (VH) genes and compared them with mouse VH genes. The The variable region of the immunoglobulin heavy chain is encoded in the germ line in three separate DNA segments: VH, DH, andJH (1-3). Three ofthe framework regions (FRs) and two of the complementarity-determining regions (CDRs) are included in the coding region of the VH segment whereas recombination between variable (V), diversity (D), and joining (J) segments is necessary to form the expressed VH gene. It is likely that there are several hundred VH gene segments organized in tandem with spacers of 8-15 kilobases (4-6). The multitude of V region amino acid sequences has been subdivided into subgroups that show a higher extent of homology and linkage between some amino acids along the chain (7-9). However, comparison of the amino acid sequences of mouse and human VH does not always allow the affiliation of V regions from the different species to homologous subgroups (10); the DNA sequences of the VH genes may provide a better tool for comparison of homologous subgroups in various species. Hybridization with VH DNA probes showed a correlation between the extent of cross-hybridization and VH gene subgroups (11). It VH families (11) and comparison of VH genes from different species will increase our understanding of the structural features that characterize a subgroup in coding and noncoding regions. We isolated human germ-line VH genes by cross-hybridization with mouse VHII genes (6). The DNA sequence shows that the human genes are homologous to human VHI (subgroup I), as defined by Kabat et al. (14) and we will refer to the human genes analyzed here as human VHII genes. The homology between mouse and human VHII genes is preserved in the size [84 base pairs (bp)] and also in the sequence ofthe intron present at codon 4. Another VH gene subgroup (VHIII) contains a longer intron (102 bp) in both mouse and human (11). The homology in both intron and framework codons between mouse and human genes of the same subgroup is greater than between VH genes ofdifferent subgroups in the same species. The sequence also suggests that DNA repeats at the 5' and 3' regions flanking the VH gene can form a large stem-and-loop structure that may facilitate saltatory replication (15