Developmental Transitions in C. elegans Larval Stages - Current Topics in Developmental Biology - page 151

CHAPTER SIX

Developmental Transitions
in C. elegans Larval Stages

Ann E. Rougvie * ,1 , Eric G. Moss †
* Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota,
USA
† Department of Molecular Biology, Rowan University, Stratford, New Jersey, USA
1

Corresponding author: e-mail address: [e-mail]

Contents
1.

Introduction 154

2. A Worm Well-Suited to Timing Studies 154

3. Heterochronic Mutants 156

4. microRNA Switches 159

5. LIN-28: A microRNA Regulator at the Pathway's Center 160

6. The Heterochronic Pathway 161

7. Developmental Transitions: The Molts 162

8. LIN-42: A Link Between Molting and Developmental Decisions 164

9. Reversible Interruption of Developmental Progression: DAF-12 167

10. Interrupted Development: Reprogramming and Resynchronization 169

11. Launching Larval Development 171

12. A Heterochronic Pathway for Larger Animals? 173

13. Conclusions and Future Directions 173

Acknowledgments 174

References 175

Abstract
Molecular mechanisms control the timing, sequence, and synchrony of developmental
events in multicellular organisms. In Caenorhabditis elegans, these mechanisms are rev-
ealed through the analysis of mutants with “heterochronic” defects: cell division or dif-
ferentiation patterns that occur in the correct lineage, but simply at the wrong time.
Subsets of cells in these mutants thus express temporal identities normally restricted
to a different life stage. A seminal finding arising from studies of the heterochronic
genes was the discovery of miRNAs; these tiny miRNAs are now a defining feature of
the pathway. A series of sequentially expressed miRNAs guide larval transitions through
stage-specific repression of key effector molecules. The wild-type lineage patterns are
executed as discrete modules programmed between temporal borders imposed by the
molting cycles. How these successive events are synchronized with the oscillatory
molting cycle is just beginning to come to light. Progression through larval stages