Worm Breeder's Gazette 13(3): 85 (June 1, 1994)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

daf-12 (= mig-7 )mutations cause heterochronic delays in cell migration and cell lineage, and perturb dauer formation.

Adam Antebi, Ed Hedgecock

Johns Hopkins University, Department of Biology, Baltimore, MD, 21218.

Previously described heterochronic genes lin-4 , lin-14 , lin-28 ,and lin-29 have no effect on the timing of gonadal development (Ambros and Horvitz (1984), Science 226, 409). We have characterized two genes designated mig-7 and mig-8 that apparently function in the temporal program of gonadogenesis. Mutations in these genes result in altered direction, a delay in or premature cessation of trajectories taken by the migratory gonadal leader cells, i.e. the hermaphrodite distal tip cells and the male linker cell, giving rise to altered gonad morphogenesis (Mig phenotype). In severe alleles of mig-7 and mig-8 ,the distal tip cells fail in dorsal reflexion, and correlatively do not express the unc-5 dorsal guidance receptor at the appropriate stage (J. Cullotti, M.W. Su pers. com.).

mig-7 also delays stage-specific lineages in non-gonadal cell types (Lin phenotype) in a manner reminiscent of known heterochronic mutations. For example, seam cells reiterate the L1 /L2molt pattern of cell division at the L2 /L3molt. At the L4 /adultmolt occasional seam cells fail in the larval to adult switch, and undergo a round of division, giving rise to alae gaps.

We have isolated various mig-7 alleles that give rise to dauer defective (Daf-d), dauer constitutive (Daf-c), or wildtype phenotypes (Daf+). Interestingly, Mig and Lin phenotypes are suppressed by dauer development, another hallmark of heterochronic genes (Liu and Ambros (1991), Nature 350, 162). Moreover, Lin, Mig, and Daf phenotypes are genetically separable suggesting multiple functions for the mig-7 gene product.

Mapping and complementation experiments indicate that mig-7 is allelic to daf-12 ,a mutation that blocks dauer development (Daf-d phenotype). Several genetic models suggest that daf-12 mediates a terminal step in a signal transduction pathway that regulates genes expressed during dauer development (Riddle et al. (1981) Nature 290, 668-671; Vowels and Thomas (1992), Genetics 130, 105). This work now implicates daf-12 as a late-acting heterochronic gene to effect dauer morphogenesis under harsh conditions or to advance continuous development (e.g. gonadal leader cell migrations and hypodermal differentiation) under replete conditions.

Recently, daf-12 has been cloned and shown to encode a member of hormone receptor superfamily of ligand-activated transcription factors (P. Larsen, D. Riddle, pers. com.). This result may explain daf-12 'sseparable phenotypes since hormone receptors often form heterodimers or their mRNAs are alternately spliced. We would like to know what is the daf-12 ligand, and what is the source and timing of its release? What are its transcriptional partners and targets? In particular, mig-8 could be a candidate partner acting in the gonadal leader cells or mig-8 and unc-5 may be possible target genes. We have mapped mig-8 to a narrow region on X as a prelude to positional cloning.