Jym Mohler

hedgehog is a segment polarity gene necessary to maintain the proper organization of each segment of the Drosophila embryo. We have identified the physical location of a number of rearrangement breakpoints associated with hedgehog mutations. The corresponding hh RNA is expressed in a series of segmental stripes starting at cellular blastoderm in the posterior portion of each segment. This RNA is localized predominantly within nuclei until stage 10, when the localization becomes primarily cytoplasmic. Expression of hh RNA in the posterior compartment is independent of most other segment polarity genes, including en, until the late extended germ-band stage (stage 11). Sequence analysis of the hedgehog locus suggests the protein product is a transmembrane protein, which may, therefore, be directly involved in cell-cell communication.

Dominant mutations at two loci, BicaudalC (BicC) and BicaudalD (BicD), cause heterozygous females to produce double-abdomen embryos. These mutations cause the production of embryos with a range of defects extending from the anterior end of the differentiated embryo. The same array of defective embryos is caused by mutations at either locus and is similar to that produced by the original mutation at bicaudal (bic). The array of defective embryos suggests that these mutations cause the loss of positional values from the anterior end of the embryo, associated with a duplication of the posterior end if too few positional values remain. BicaudalD mutations appear to be antimorphic, gain-of-function mutations, whereas BicaudalC mutations are likely to be hypomorphic or amorphic mutations. Mutations at all these loci (bic, BicC and BicD) act as mutual enhancers of each other, and a number of other maternal-effect mutations also act to either enhance or suppress the expression of these dominant bicaudal mutations.

The expression pattern and DNA sequence of a newly identified gene, CNC (cap'n'collar), suggest a role for this gene in cephalic patterning during Drosophila embryogenesis. In situ hybridization reveals transcripts localized to the mandibular segment and the hypopharyngeal and labral primordia first detectable in late blastoderm stages. Sequence analysis of cDNA clones from the CNC locus shows the CNC gene product to be related to transcription factors of the leucine zipper (bZIP) class. Based on its protein sequence, we propose that CNC is a subunit of a heterodimeric regulatory protein involved in the control of head morphogenesis.

Mutational analysis of cap'n'collar (cnc), a bZIP transcription factor closely related to the mammalian erythroid factor NF-E2 (p45), indicates that it acts as a segment-specific selector gene controlling the identity of two cephalic segments. In the mandibular segment, cnc has a classical homeotic effect: mandibular structures are missing in cnc mutant larvae and replaced with duplicate maxillary structures. We propose that cnc functions in combination with the homeotic gene Deformed to specify mandibular development. Labral structures are also missing in cnc mutant larvae, where a distinct labral primordia is not properly maintained in the developing foregut, as observed by the failure to maintain and elaborate patterns of labral-specific segment polarity gene expression. Instead, the labral primordium fuses with the esophageal primordium to contribute to formation of the esophagus. The role of cnc in labral development is reciprocal to the role of homeotic gene forkhead, which has an identical function in the maintenance of the esophageal primordium. This role of homeotic selector genes for the segment-specific maintenance of segment polarity gene expression is a unique feature of segmentation in the preoral head region of Drosophila.