BMP signaling determines body size via transcriptional regulation of collagen genes in caenorhabditis elegans

Uday Madaan, Edlira Yzeiraj, Michael Meade, James F. Clark, Christine Rushlow, Cathy Savage-Dunn

Research output: Contribution to journalArticle

Abstract

Body size is a tightly regulated phenotype in metazoans that depends on both intrinsic and extrinsic factors. While signaling pathways are known to control organ and body size, the downstream effectors that mediate their effects remain poorly understood. In the nematode Caenorhabditis elegans, a Bone Morphogenetic Protein (BMP)-related signaling pathway is the major regulator of growth and body size. We investigated the transcriptional network through which the BMP pathway regulates body size and identified cuticle collagen genes as major effectors of growth control. We demonstrate that cuticle collagens can act as positive regulators (col-41), negative regulators (col-141), or dose-sensitive regulators (rol-6) of body size. Moreover, we find a requirement of BMP signaling for stage-specific expression of cuticle collagen genes. We show that the Smad signal transducers directly bind conserved Smad-binding elements in regulatory regions of col-141 and col-142, but not of col-41. Hence, cuticle collagen genes may be directly and indirectly regulated via the BMP pathway. Our work thus connects a conserved signaling pathway with its critical downstream effectors, advancing insight into how body size is specified. Since collagen mutations and misregulation are implicated in numerous human genetic disorders and injury sequelae, understanding how collagen gene expression is regulated has broad implications.

Original languageEnglish (US)
Pages (from-to)1355-1367
Number of pages13
JournalGenetics
Volume210
Issue number4
DOIs
StatePublished - Dec 1 2018

Fingerprint

Bone Morphogenetic Proteins
Caenorhabditis elegans
Body Size
Collagen
Genes
Intrinsic Factor
Inborn Genetic Diseases
Organ Size
Gene Regulatory Networks
Nucleic Acid Regulatory Sequences
Medical Genetics
Growth
Transducers
Phenotype
Gene Expression
Mutation
Wounds and Injuries

Keywords

  • BMP
  • Body size
  • C.Elegans
  • Collagen
  • Growth

ASJC Scopus subject areas

  • Genetics

Cite this

BMP signaling determines body size via transcriptional regulation of collagen genes in caenorhabditis elegans. / Madaan, Uday; Yzeiraj, Edlira; Meade, Michael; Clark, James F.; Rushlow, Christine; Savage-Dunn, Cathy.

In: Genetics, Vol. 210, No. 4, 01.12.2018, p. 1355-1367.

Research output: Contribution to journalArticle

Madaan, Uday ; Yzeiraj, Edlira ; Meade, Michael ; Clark, James F. ; Rushlow, Christine ; Savage-Dunn, Cathy. / BMP signaling determines body size via transcriptional regulation of collagen genes in caenorhabditis elegans. In: Genetics. 2018 ; Vol. 210, No. 4. pp. 1355-1367.
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