TY - JOUR
T1 - Novel gain-of-function alleles demonstrate a role for the heterochronic gene lin-41 in C. elegans male tail tip morphogenesis
AU - Del Rio-Albrechtsen, Tania
AU - Kiontke, Karin
AU - Chiou, Shu Yi
AU - Fitch, David H A
N1 - Funding Information:
We thank C. Seideman for helping with SNP mapping and RNAi tests of candidate genes and D. Tranchina for help with statistical analyses. We are indebted to J. Hubbard, C. Desplan, S. Lall, J. Nance, and two anonymous reviewers for helpful comments and suggestions. We thank F. Slack for reagents. For strains, we thank S. Emmons, A. Rougvie, S. Takagi, and the Caenorhabditis Genetics Center, which is supported by the NIH NCRR. For technical assistance, we thank T. Hadi. This work was supported by NSF grants 9506844, 9981632, and 0228692.
PY - 2006/9/1
Y1 - 2006/9/1
N2 - To gain an understanding of the genes and mechanisms that govern morphogenesis and its evolution, we have analyzed mutations that disrupt this process in a simple model structure, the male tail tip of the rhabditid nematode C. elegans. During the evolution of rhabditid male tails, there have been several independent changes from tails with rounded tips ("peloderan", as in C. elegans) to those with pointed tips ("leptoderan"). Mutations which produce leptoderan (Lep) tails in C. elegans thus identify candidate genes and pathways in which evolutionary changes could have produced leptoderan tails from peloderan ancestors. Here we report that two novel, gain-of-function (gf) alleles of lin-41 have lesions predicted to affect the N-terminus of the RBCC-domain LIN-41 protein. Both gf alleles cause the tail tip of adult males to retain the pointed shape of the juvenile tails, producing a Lep phenotype that looks like the tails of leptoderan species. Consistent with its role in the heterochronic pathway, we find that lin-41 governs the timing and extent of male tail tip morphogenesis in a dose-dependent manner. Specifically, the Lep phenotype results from a heterochronic delay in the retraction and fusion of the tail tip cells during L4 morphogenesis, such that retraction is not completed before the adult molt. Conversely, we find that tail tip morphogenesis and cell fusions begin precociously at the L3 stage in the reduced-function lin-41 mutant, ma104, resulting in over-retracted male tails in the adult. Because modulated anti-LIN-41 RNAi knockdowns in the gf mutants restore wild-type phenotype, we suggest that the leptoderan phenotype of the gf alleles is due to a higher activity of otherwise normal LIN-41. Additionally, the gf allele is suppressed by the wild-type allele, suggesting that LIN-41 normally regulates itself, possibly by autoubiquitination. We speculate that small changes affecting LIN-41 could have been significant for male tail evolution.
AB - To gain an understanding of the genes and mechanisms that govern morphogenesis and its evolution, we have analyzed mutations that disrupt this process in a simple model structure, the male tail tip of the rhabditid nematode C. elegans. During the evolution of rhabditid male tails, there have been several independent changes from tails with rounded tips ("peloderan", as in C. elegans) to those with pointed tips ("leptoderan"). Mutations which produce leptoderan (Lep) tails in C. elegans thus identify candidate genes and pathways in which evolutionary changes could have produced leptoderan tails from peloderan ancestors. Here we report that two novel, gain-of-function (gf) alleles of lin-41 have lesions predicted to affect the N-terminus of the RBCC-domain LIN-41 protein. Both gf alleles cause the tail tip of adult males to retain the pointed shape of the juvenile tails, producing a Lep phenotype that looks like the tails of leptoderan species. Consistent with its role in the heterochronic pathway, we find that lin-41 governs the timing and extent of male tail tip morphogenesis in a dose-dependent manner. Specifically, the Lep phenotype results from a heterochronic delay in the retraction and fusion of the tail tip cells during L4 morphogenesis, such that retraction is not completed before the adult molt. Conversely, we find that tail tip morphogenesis and cell fusions begin precociously at the L3 stage in the reduced-function lin-41 mutant, ma104, resulting in over-retracted male tails in the adult. Because modulated anti-LIN-41 RNAi knockdowns in the gf mutants restore wild-type phenotype, we suggest that the leptoderan phenotype of the gf alleles is due to a higher activity of otherwise normal LIN-41. Additionally, the gf allele is suppressed by the wild-type allele, suggesting that LIN-41 normally regulates itself, possibly by autoubiquitination. We speculate that small changes affecting LIN-41 could have been significant for male tail evolution.
KW - Caenorhabditis elegans
KW - Evolution
KW - Heterochronic
KW - Male tail
KW - Morphogenesis
KW - Oscheius
KW - RBCC
KW - let-7
KW - lin-41
UR - http://www.scopus.com/inward/record.url?scp=33748078460&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748078460&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2006.04.472
DO - 10.1016/j.ydbio.2006.04.472
M3 - Article
C2 - 16806150
AN - SCOPUS:33748078460
SN - 0012-1606
VL - 297
SP - 74
EP - 86
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -