| First Author | Studer M | Year | 1994 |
| Journal | Genet Res | Volume | 63 |
| Issue | 2 | Pages | 157 (Abstr) |
| Mgi Jnum | J:18695 | Mgi Id | MGI:66936 |
| Citation | Studer M, et al. (1994) Positive and negative regulation of the segment-restricted expression of the Hox-b1 gene in the developing hindbrain. Genet Res 63(2):157 (Abstr) |
| abstractText | Full text of Abstract: Positive and negative regulation of the segment-restricted expression of the Hox-b1 gene in the developing hindbrain. MICHELE STUDER, HEATHER MARSHALL AND ROBB KRUMLAUF Lab. of Developmental Neurobiology, NIMR, The Ridgeway, Mill Hill, London NW7 1AA, UK. We are interested in the cellular and molecular mechanisms which govern the establishment and maintenance of rhombomeric segments in the developing vertebrate hindbrain. To address this problem at the molecular level we have identified the cis-acting regulatory regions of the Hox-bl gene which are involved in modulating its rhombomere-restricted expression in transgenic mice. We have used these mice to perform a detailed investigation on how the cellular patterns of expression are established. There is a broad and diffuse initial domain of expression with no clearly defined cellular boundaries. This pattern sharpens and becomes progressively restricted to the future r4. Deletion analysis was initially performed on a 7.5 kb Hox-b1/lacZ construct which reproduces the normal r4 restricted domain of expression and responds to retinoic acid. We have found that a 1.6 kb fragment on the 5' flanking region is capable of directing both the r4 and retinoic acid response on a heterologous promoter. More extensive deletion analysis has defined two separate regions which interact to generate the r4 restricted expression. One is a 600 bp enhancer which simulates expression in a domain largely confined to r4, but with some expression extending into adjacent rhombomeres. There is a high degree of sequence identity within this region in the chicken Hox-bl gene which suggests that regulatory regions may be conserved between these species. To test this we have generated transgenic mice with these chick sequences and shown that they function in a similar manner. Sequence analysis reveals several conserved motifs shared between these species. The second region acts as a negative component and is necessary to restrict the expression of the transgene, stimulated by the 600 bp enhancer, solely to r4. Therefore we believe this region is involved in mediating the normal process which leads to the progressive restriction of Hox-bl expression in r4. We conclude that a combination of positive and negative regulation is needed to generate the segment-restricted patterns of Hox expression in the hindbrain. |
