KROX-20 - A CANDIDATE GENE FOR THE REGULATION OF PATTERN-FORMATION IN THE HINDBRAIN

The mouse gene Krox-20 was isolated on the basis of cross-hybridization with Kruppel, a Drosophila segmentation gene. During recent years, an accumulation of structural, biochemical and expression data has indicated that Krox-20 encodes a transcription factor which may play a key role within a regulatory network involved in pattern formation in the developing hindbrain. The DNA-binding domain of Krox-20 consists of 3 zinc fingers and the protein recognizes a specific GC-rich nucleotide sequence. It can activate the transcription of genes located in the vicinity of this sequence. Krox-20 transcription itself is modulated by growth factors. During formation of the vertebrate central nervous system (CNS), the hindbrain is organized into segmental units, called rhombomeres. Prior to the appearance of morphological segmentation, Krox-20 is expressed in 2 stripes within the hindbrain. Later on, the Krox-20 expression domains match with 2 alternate rhombomeres. These data suggest that Krox-20 may regulate aspects of the segmentation process. The observation of segment-specific expression boundaries for homeobox containing genes in the hindbrain suggests that these genes may also be part of the regulatory network governing pattern formation in this region of the CNS. The possible interactions between Krox-20 and homeobox containing genes as well as the search for other members of the network will be discussed.