Peter Gruss

Do multigene families regulate vertebrate development

The identification of mammalian gene families sharing protein domains with genes that regulate Drosophila embryogenesis could prove to be a major stepping stone towards understanding the genetic basis of mammalian development. Three types of multigene families have already been identified whose expression patterns during embryogenesis are strikingly different from one another. Evidence is accumulating that these multigene families may participate in pattern formation and segmentation of the mammalian embryo.

Pax genes in development

SUMMARY The Pax gene family consists of nine members encoding nuclear transcription factors. Their temporally and spatially restricted expression pattern during embryogenesis suggests that they may play a key role during embryogenesis. Direct evidence for the important role of the Pax genes during embryonic development has been demonstrated by the correlation of mouse developmental mutants and human syndromes with mutations in some Pax genes. To date three Pax genes have been shown to be mutated in undulated, Splotch and small eye, respectively. In man, Pax-3 is mutated in the Waardenburg syndrome, while in aniridia Pax-6 is mutated.

Making of a Schwann

COMMENT vectors are based on the single-strand DNA non-enveloped parvovirus. Cur- rently, this vector has a rather small ~pacity (4.5-5.0 kb) to express trans- genes. While wild-type AAV has been documented to establish latency, by targeting integration to chromosome 19, much i.,fformation remains to be determined about this vector con- ceming,he relative importance of ex- pression from episomal versus inte- grated forms. In addition, require- ments for conversion from single to double-strand DNA structures for ex- pression suggest a unique aspect spe- cific to this vector system. However, an absence of detectable toxicity and evidence of wide-spread cellular up- take of AAV vectors has been re- ported in preclinical evaluations of AAV (Ref. 24). What is clear from our previous experience with gene therapy for CF is that the testing of candidate gene therapy vectors must be performed in relevant airway test systems (i.e. only highly differentiated columnar cell systems

Murine Hox Genes — A Multigene Family

The embryonal development of higher organisms is conducted by a network of many different structural and regulatory gene functions whose complexity is yet poorly understood. Some genetic elements identified as being involved in specifying segment identity of the fruit fly Drosophila melanogaster are the homeotic genes (Ouweneel 1976). Several homeotic genes of Drosophila belonging to either the engrailed gene complex (EN-C; Garcia-Bellido and Santamaria 1972) or the antennapedia and bithorax complex (ANT-C/BX-C; Regulski et al. 1985) contain a 180 bp conserved region, the “homeo box”, coding for a protein domain of the helix-turn-helix type (McGinnis et al. 1984a, b; Scott and Weiner 1984). This type of DNA-binding domain was first detected in procaryotes. Interestingly, the two yeast mating-type proteins MAT a-1 and MAT α2 (Shepherd et al. 1984; Laughon and Scott 1984) show significant similarities to the consensus homeodomain sequence. MAT α2 is a transcriptional repressor (Wilson and Hershkowitz 1984; Hartig et al. 1986). It was therefore hypothesized that the Drosophila homeodomain proteins might also have regulatory functions, e.g., by interacting directly or indirectly in trans with their own promoter regions or those of other genes (Desplan et al. 1985).