The nuclear receptor gene nhr-25 plays multiple roles in the Caenorhabditis elegans heterochronic gene network to control the larva-to-adult transition

• Published in: Developmental biology Vol. 344; no. 2; pp. 1100 - 1109
• Main Authors: Hada, Kazumasa, Asahina, Masako, Hasegawa, Hiroshi, Kanaho, Yasunori, Slack, Frank J., Niwa, Ryusuke
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-08-2010
• Subjects: Animals; apl-1; Caenorhabditis - genetics; Caenorhabditis - metabolism; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - physiology; Cell Differentiation - genetics; Cell Division; developmental timing; Gene Regulatory Networks; heterochronic gene; Larva - genetics; Larva - metabolism; let-7; MicroRNAs - genetics; MicroRNAs - metabolism; Mutation; nhr-25; nuclear receptor; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Caenorhabditis elegans; developmental timing; let-7; nuclear receptor; apl-1; nhr-25; heterochronic gene
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2010.05.508

Developmental timing in the nematode
Caenorhabditis elegans is controlled by heterochronic genes, mutations in which cause changes in the relative timing of developmental events. One of the heterochronic genes,
let-7, encodes a microRNA that is highly evolutionarily conserved, suggesting that similar genetic pathways control developmental timing across phyla. Here we report that the nuclear receptor
nhr-25, which belongs to the evolutionarily conserved
fushi tarazu-factor 1/nuclear receptor NR5A subfamily, interacts with heterochronic genes that regulate the larva-to-adult transition in
C. elegans. We identified
nhr-25 as a regulator of
apl-1, a homolog of the Alzheimer's
amyloid precursor protein-like gene that is downstream of
let-7 family microRNAs. NHR-25 controls not only
apl-1 expression but also regulates developmental progression in the larva-to-adult transition. NHR-25 negatively regulates the expression of the adult-specific collagen gene
col-19 in lateral epidermal seam cells. In contrast, NHR-25 positively regulates the larva-to-adult transition for other timed events in seam cells, such as cell fusion, cell division and alae formation. The genetic relationships between
nhr-25 and other heterochronic genes are strikingly varied among several adult developmental events. We propose that
nhr-25 has multiple roles in both promoting and inhibiting the
C. elegans heterochronic gene pathway controlling adult differentiation programs.